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LIU Xihong, DU Xiaodan, FAN Mengyang, XU Liuqing, ZHAO Peiyuan
2023,31(6):697-705, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 001
Abstract:
Objective To observe the effect of miR-328-3p on the growth and apoptosis of glioma cells, and explore the role and mechanism of the miR-328-3p-Akt/ mTOR axis in inhibition of glioma cell growth by triptolide using U251 cells and a xenograft model in nude mice. Methods miR-328-3p overexpression were induced after treatment of with triptolide in U251 cells. qRT-PCR, CCK-8, colony formation assays, flow cytometry, and Western Blot were performed to assess the role of miR-328-3p in inhibition of U251 cells by triptolide. A xenotransplanted tumor model was established with stable miR-328-3p expression to verify the role of miR-328-3p in inhibition of glioma cells by triptolide using qRT-PCR and small animal imaging in vivo. Results miR-328-3p expression in glioma cells and tissues was decreased, and its expression level was positively correlated to the overall survival rate of patients with primary and recurrent glioma. the Akt/ mTOR signaling pathway. Conclusions miR-328-3p is a tumor suppressor gene in glioma. Triptolide promotes apoptosis of glioma cells, inhibits activation of the Akt/ mTOR signal pathway, and inhibits glioma cell growth through miR-328-3p.
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CHANG Surui, LIU Jiangang, WEN Jiayu, LI Hao, DONG Guoju, LIU Chunqiu, SHI Yujiao
2023,31(6):706-714, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 002
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Objective To observe changes on pathological morphology and iron content in brain tissue of spontaneously hypertensive rats (SHR) with multiple risk factors (high fat, salt, and carbohydrate diets). Methods Fourteen-week-old SPF grade, 8 rats in each group, normal control group(share the same genetic background, the WKY group). SHR rats were randomly divided into four groups: control group (SHRs group), high fat diet group (HFAT-SHRs group), high salt diet group (HSAIL-SHRs group), and high glucose and fat diet group (DM-SHRs group was established by intraperitoneal injection of 1% streptozotocin. And at the same time and blood glucose content was kept above 11. 1 mmol/ L was regarded to be the diabetes model standard). WKY group and SHRs group was fed an ordinary diet, and the model groups were fed high fat, salt, or sugar diets. The treatments were carried out for 32 weeks. Changes in iron content in serum and brain tissue were measured, pathological morphology and iron content (Prussian blue staining) of brain tissue were observed under a light microscope, and the levels of inflammatory factors, and cholinergic and β-AP contents were measured by ELISA. Results Compared with the WKY group, brain cells in each model group showed a disordered arrangement, nuclear pyrosis, and decreased or absent Nissl bodies. Iron staining showed expansion of the iron area, especially in the DM-SHRs group. ACh and AChE contents in the SHRs group and three model groups were decreased, while IL-1β and IL-6 contents were increased (P< 0. 05, P< 0. 05), and iron content in serum and brain tissue was increased (P< 0. 05, P< 0. 05). There was no statistical significance within groups (P> 0. 05). Conclusions High fat, salt, and sugar are factors that change the morphology of brain cells, promote iron deposition, and inhibit endogenous antioxidant activity. Iron overload may lead to cognitive impairment by hypertensive brain damage.
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WANG Huihui, GUO Chenbo, TAN Dengxu, ZHANG Yanying, WANG Yongfeng, SHI Changhong
2023,31(6):715-721, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 003
Abstract:
Objective To study the effect of curcumin (Cur) combined with monoamine oxidase A (MAOA) inhibitor clorgyline ( Clo) on lung cancer cell proliferation and its mechanism. Methods The effect of various concentrations of Cur and Clo on proliferation of the lung cancer cell line H460 was assessed by a CCK-8 assay. Western Blot was used to analyze the effect of Cur, Clo, and Cur combined with Clo on MAOA expression in H460 cells. The inhibitory effect of Cur, Clo, and Cur combined with Clo on H460 cell proliferation was further examined in a xenograft model in nude mice. Immunohistochemistry was used to assess the effect of Clo on Ki67 protein expression in tumor tissue of the xenograft model. TUNEL staining was used to detect apoptosis in various treatment groups of xenografted tumor tissue. Results Cur, Clo, and Cur combined with Clo inhibited H460 cell proliferation in a dose-dependent manner and H460 cell growth in the xenograft model (P< 0. 01), decreased the Ki67 expression, and increased apoptosis. Importantly, the combined treatment group showed more significant inhibitory effects (P< 0. 01). Conclusions Cur combined with Clo inhibits the proliferation of H460 lung cancer cells, which may be related to reducing expression of the cell proliferation protein Ki67 and increasing apoptosis.
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QIU Huaming, LI Zixiang, JIN Yuanqing, WU Shuguang
2023,31(6):722-732, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 004
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Objective To explore the intrinsic biomaterial basis of the TCM syndrome of type 2 diabetes in adult SD rats through differential metabolic markers and metabolic pathways using urine untargeted metabolomics. Methods SD rats were randomly divided into normal and T2DM groups with deficiency of both qi and yin. The T2DM group with deficiency of both qi and yin was established by feeding a high fat and sugar diet combined with intraperitoneal injection of a small dose of streptozotocin (35 mg/ kg) and intragastric administration of Qingpi Fuzi powder granules. Untargeted metabonomic analysis of urine was performed by liquid chromatography-tandem mass spectrometry. Potential biomarkers and pathway enrichment were identified by principal component analysis, partial least squares discriminant analysis, KEGG database, HMDB database, LIPIDMaps database, and MS/ MS tandem ion fragment information. Results Metabolite changes related to diabetes were found to involve nine carbohydrate, twelve lipid, nine amino acid, and two energy metabolic pathways. Conclusions There are carbohydrate, lipid, amino acid, and bioenergy metabolism disorders in the biological model of qi yin deficiency in diabetes. Metabonomics are helpful to reveal the material basis of TCM syndromes.
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SHEN Haotian, JIANG Junjie, CHAO Ying, HONG Min, ZHENG Jie, BIAN Huimin
2023,31(6):733-742, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 005
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Objective To investigate whether postmenopausal lipid metabolism disorder is involved in the development of depressive symptoms. Methods Twenty-four LDLR-/ - and sixteen WT C57BL/6J female mice were divided into five groups (n= 8): WT + normal diet group(WT), WT + high-fat diet group(WT-H), ovariectomized LDLR-/ - +normal diet group(LDLR-/ - ), ovariectomized LDLR-/ - + high-fat diet group(LDLR-/ - -H), and ovariectomized LDLR-/ - +high-fat diet + simvastatin group(XF). Mice were fed continuously for 3 months. The postmenopausal lipid metabolism disorder model was established in LDLR-/ - female mice after bilateral ovariectomy combined with a high-fat diet. Body weight, total cholesterol (TC), ERα, and ERβ levels in the hippocampus, depressive behavior, and 5-HT levels in the brain were determined. The correlation between the brain TC level and depression-related indexes was analyzed. Results (1)The LDLR-/ - -H group successfully replicated the characteristics of postmenopausal lipid metabolism disorder, which showed a significant increase in body weight, a notable increase in the brain TC level, and a significant decrease in expression of ERβ in the hippocampus. (2) Horizontal and vertical locomotor activities of the LDLR-/ - -H group were significantly decreased, the immobilized time of TST was significantly increased, and the brain 5-HT level was significantly decreased. (3) The brain TC level of the XF group was significantly decreased, depressive behavior was significantly improved, and the 5-HT level was significantly increased. (4) Correlation analysis showed that the TC level in the brain was significantly correlated to the 5-HT level and depression-like behaviors. Conclusions Postmenopausal lipid metabolism disorder induces depressive symptoms, and depression symptoms can be significantly improved by regulating lipid metabolism disorder.
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XU Lei, LUO Xiaoquan, QU Ping, ZHONG Yi, ZHANG Hong, ZENG Xianbao, YANG Yuyan, LIU Zhiyong, HONG Tao
2023,31(6):743-755, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 006
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Objective To compare changes in microbial diversity in the intestines of male and female rats with obesity and depression. Methods An obesity and depression model was established by feeding rats a high fat diet and the cums classic depression making method. SD rats were randomly divided into control group (Group C), obese group (Group F), the depression group (Group Y), the obesity and depression group (Group FY). Five months were required for modeling. Depression-like behavior was evaluated by the sugared water preference test, open field test, and forced swimming test. The serum estrogen level and blood lipids were measured. Fecal samples were also collected. Highthroughput sequencing of 16S rDNA was performed and the result were analyzed by bioinformation analysis software. Changes in intestinal flora diversity of rats in each group were compared. Results Obesity depression model rats were successfully established by a high-fat diet and cums method in the same countries. The estrogen level of obesity and obesity depression female rats was significantly increased, while there no significant difference was observed in the estrogen level between male groups. There was a significant difference in diversity of intestinal flora in Group FY. The B/ F value was lower than that of in obesity and depression groups, and the B/ F value of obesity and depression in male rats was only approximately half that of female rats. At the genus level, changes in Blautia and the other eight flora in the Group FY and Group F of male and female rats were consistent, but changes in a small number of flora in Bacteroides and other genera in females and males were inconsistent. In the male and female obesity and depression model, there were differences in the composition of Gram-positive and -negative bacteria among the intestinal flora. The composition of G+ was Firmicutes and actinomycetes, but the proportions were different. G- males mainly had Firmicutes, Bacteroides, and desulfitobacteria, whereas females mainly had Bacteroides, verruciformis, and desulfitobacteria with different composition ratios. Conclusions Significant changes in the composition and structure of intestinal flora in male and female obese and depressed rats may be related to estrogen.
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HE Yue, SUN Maomao, WU Congrong, YU Yonghui
2023,31(6):756-762, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 007
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Objective To establish a rat model of hypertensive disorder complicating pregnancy (HDCP) and observe the effect of HDCP on thyroid morphology and function in preterm rats at various gestational ages. Methods Tenweek-old SD pregnant rats were randomly divided into control and HDCP groups. Rats in the HDCP group were subcutaneously injected with L-nitroarginine methyl ester (L-NAME; 250 mg/ (kg·d)). Rats in the control group were subcutaneously injected with the same volume of normal saline. Preterm rats were obtained by cesarean section at 18 ~ 21 days of gestation. Body weight and length of the preterm rats were recorded. The liver and thyroid gland were isolated, thyroid hormone levels were measured in a liver homogenate, and thyroid morphology and ultrastructure were observed. Results Compared with the control group, blood pressure and urinary proteins of rats were significantly increased in the HDCP group (P< 0. 05). The weight and length of premature rats in the HDCP group were significantly lower than those in the control group (P< 0. 01). Compared with the control group, the TSH level of premature rats was significantly increased in the HDCP group on days 19, 20, and 21 (P< 0. 01), and there was no significant difference in T3 and T4 levels. HE staining showed that the follicular cavity appeared at 18 days of gestation in the control group, whereas the follicular cavity appeared at 19 days of gestation in the HDCP group, and the number of follicular lumens was decreased significantly. Transmission electron microscopy showed that the rough endoplasmic reticulum in the HDCP group was significantly swollen and degranulated, which were accompanied by retention. Conclusions An HDCP rat model was established successfully. Compared with the control group, premature rats in the HDCP group had intrauterine growth restriction, hypothyroidism, and delayed thyroid histological development, which may be caused by endoplasmic reticulum dysfunction.
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HU Ge, MA Xinyu, QIN Fei, CAO Jianmin, DONG Li, ZHOU Haitao, HUA Bing
2023,31(6):763-769, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 008
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Objective To investigate the mechanism of resveratrol protecting exercise-induced liver injury in rats. Methods Thirty-two 7-week-old male SPF SD rats were randomly divided into a control group (Group C), resveratrol RM) with eight rats in each group. Group C and Group R did not undergo any exercise. Group M and Group RM underwent 4 weeks of high-intensity treadmill training (10° slope; velocity started from 10 m/ min, which was increased by 5 m/ min every 5 min and would not increase until 35 m/ min, and then the rats were trained to exhaustion). One hour before training, Group R and Group RM were intragastrically injected with 150 mg/ (kg·bw) resveratrol in 5 mL/ (kg·bw). Group C and Group M were injected with an equal volume of solvent at the same time point. Rats were sacrificed at 24 hours after the end of the last training session, and blood and liver were collected. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity were detected by an automatic biochemical analyzer. Hepatic histomorphology was observed by hematoxylin-eosin (HE) staining. Hepatic nuclear factor-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), apoptosis-related protein B-cell lymphoma-2 (Bcl-2), and bcl-2-associated X protein (Bax) protein expression was detected by immunohistochemistry. Hepatic apoptosis was detected by TdT-mediated dUTP nick-end labeling. Hepatic superoxide dismutase (SOD) and malondialdehyde (MDA) activity was detected by colorimetry. Results Compared with Group M, serum ALT, AST activity, the hepatic MDA level, and hepatic apoptosis were significantly decreased in Group RM (P< 0. 05 or P< 0. 01), hepatic Nrf2 and HO-1 protein expression, SOD activity, the and Bcl-2/ Bax ratio were increased significantly (P< 0. 05 or P< 0. 01), and liver histopathological changes had effectively improved. Conclusions Four weeks of resveratrol treatment alleviates exercise-induced liver injury in rats, and the mechanism of its protective effect might be related to activation of the Nrf2 signaling pathway, which relieved oxidative stress in the liver, thereby antagonizing excessive occurrence of apoptosis induced by oxidative stress.
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LIU Guojun, LIU Yangchun, LIU Zhiqiang
2023,31(6):770-777, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 009
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Objective To investigate the effect of μ opioid receptor (μRs) blockers on the exercise ability and behavior of learned helplessness mice. Methods Mice were randomly divided into a learning-regression group, conjugate group, and control group. Before the mice learned to avoid the electric shock stimulus experiment, the μRs blocker β-FNA or normal saline (Sal) was used to predict the treatment. Mouse movement distances in the open field experiment were compared by T test to determine the effect of the intervention on the mobility of mice. The helplessness behavior of mice after blocking μRs was investigated by shuttling box, forced swimming, elevated cross maze, and open field experiments. Results There was no significant difference in exercise distance between the two groups compared with the control group. There was no difference in the time of electric shock between the two treatment groups during the three-day learning period. There was a significant difference between the two treatment groups for the total number of times touching the nasal contact devices on the second and third days (P< 0. 001). Conclusions The μRs blocker had no effect on the exercise ability of learned helplessness mice, and μRs played an important role in the formation of aversive behavior in mice.
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WU Yue, WANG Jue, FENG Tingting, LI Yitong, XUE Jing, GUO Jianguo, XIANG Zhiguang, HE Jun, WANG Kai, ZHANG Yang, LI Lu, GAO Hong, WEI Qiang, KONG Qi
2023,31(6):778-786, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 010
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Objective To systematically sort and integrate literature on drug screening and evaluation data based on cell and animal models, extract important fields, and construct an animal model drug screening database. Methods We formulated animal model drug screening data collection forms and collection specifications, retrieved animal model drug screening literature in accordance with the retrieval strategy, extracted keywords and data, pretreatment, integration, and analysis, visually displayed the drug screening experimental data. Results The animal model drug screening database was mainly based on cell and animal model drug evaluation experiments, covering basic information, experimental grouping, experimental method, animal phenotypes, and drug evaluation information, and visualizing the phenotypic data. A total of 691 animal model drug screening experimental datasets were obtained, which realized the integration and sharing of animal model drug screening experimental data. Conclusions We established an animal model drug screening database, mainly based on cell and animal data to provide data support for drug screening and promote data-driven biomedical innovation research and novel drug discovery.
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2023,31(6):787-794, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 011
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Atherosclerosis (AS) is the pathological basis of common cardiovascular diseases such as heart disease and stroke, and its causative factors are complex and diverse. With the advancement of mature genetic modifications, mouse models have provided an important basis to study the pathogenesis of AS and validating drug efficacy. In this article, we review the pathological characteristics of traditional transgenic and novel mouse models on the basis of lipoprotein metabolism and histopathological changes, as well as their potential and limitations for preclinical application in drug development, so that future studies on mechanisms related to this disease can be targeted to select models.
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LIU Hao, LI Wenjing, WANG Xinai, WANG Chenqi, WU Yaxuan, XIAO Hongling
2023,31(6):795-801, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 012
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Humans can mimic the behavior of others and produce the same emotional experiences, a phenomenon known as emotional contagion. Rodents (mainly rats and mice) are commonly used as experimental animals in medical research. These animals can also suffer from emotional contagion associated with negative emotions such as fear, anxiety, and depression. To further understand the process of the transmission of different emotions among animals, we review the definition and process of emotional contagion, as well as the influencing factors and the main types and their physiological mechanisms, to provide a reference for subsequent studies.
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ZHANG Yiwen, YAO Caihong, SUN Xinran, CHEN Shanguang, LIU Xinmin, JIANG Ning
2023,31(6):802-810, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 013
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Animal behavioral experiments are basic experimental method used to evaluate the learning and memory of animals and are widely used in physiological and pathological mechanism research and pharmacodynamic evaluation. The assessment method to evaluate the learning and memory behavior of rats can be divided into three categories by the experimental principle: punitive, spontaneous, and rewarding. On the basis of the reward principle and Skinner’ s conditional reflex principle, the reward-directed operant conditioning method provides a more comprehensive and detailed assessment method to assess advanced cognitive functions in the learning and memory of animals, which is particularly suitable to evaluate the cognitive state when performing complex operational tasks under modern high-tech conditions. This study summarizes the development process, experimental devices, experimental method, and application fields of the reward-directed operant conditioning method, providing reference for future research and the application of this method in the field of animal behavioral experiments of learning and memory in China.
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CHEN Yating, LEI Mengzhu, ZHANG Bo, LI Chuanyu
2023,31(6):811-819, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 014
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Depression is a serious mental disorder that affects a wide range and a large number of people. Pathogenic hypotheses for the condition include classical hypothalamic-pituitary-adrenocortical (HPA) axis dysfunction and monoamine and neural plasticity deficiencies. More in-depth investigations are required to fully reveal the complexities of the pathogenesis and interactions between multiple pathogenic factors. Chronic stress is the main clinical factor that induces depression; therefore, it is vital to fully reveal the complex pathological mechanisms and the changes that occur during chronic stress exposure for the rapid and effective transformation of translational findings and the efficient prevention and treatment of the disease. Existing reviews related to depression pathogenesis have mainly focused on the classical hypotheses of HPA axis dysfunction and monoamine deficiency, as well as morphological and functional abnormalities of different brain subregions, neurons, central neurotransmitters, factors, and the corresponding receptors. The present review summarizes current depression research hotspots and new findings that have surfaced in recent years, such as genetic variants and epigenetic modifications, structural and functional abnormalities of glial cells (astrocytes and microglia), mitochondrial dysfunction, and systematic abnormalities (oxidative stress, immune inflammatory response, microbial-gut-brain). This paper systematically presents the research progress made into the mechanisms underlying chronic-stress-induced depressivelike behavior in animals, to benefit further in-depth studies into the pathogenesis, and to provide novel ideas for the clinical prevention and treatment of the disease.
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FANG Wei, CHEN Fangyuan, ZHENG Jilong, YE Liutong, NIU Chengyi
2023,31(6):820-826, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 015
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Bite force is an important indicator of animal viability. Measuring canine bite force has positive implications for canine restoration, canine food, toy evaluation, police screening, and the use of dogs. Chinese research on canine bite force testing is more police personnel and dominated by product development, which rarely investigates actual measurement work. This review summarizes various method of dog bite force testing, such as the bite method, electromyography, lever model method, and finite element analysis to provide a to study dog bite force.
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HUANG Yawei, XU Tingwei, ZHANG Hao
2023,31(6):827-832, DOI: 10. 3969 / j.issn.1005-4847. 2023. 06. 016
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The flap ischemia-reperfusion injury (FIRI) animal model provides valuable information to understand the pathogenesis and treatment of necrosis after flap transplantation. Establishing a suitable FIRI animal model is a necessary prerequisite to comprehend the pathophysiology of FIRI and test novel preventive and therapeutic method. When designing an FIRI animal model, it is important to understand the characteristics, modeling method, unique performance of each animal model, and which tissue structures or functions of the selected animal model are similar to human flaps. For over half a century, researchers have used rats to establish abdominal and dorsal island flap models, rat dorsal random flap models, and some novel FIRI models. However, so far there is no ideal model that fully simulates the complex mechanism of necrosis after human flap transplantation or its prevention and treatment method. Therefore, this review summarizes the most commonly used rat models to establish FIRI models, which may facilitate choosing suitable parts and method for modeling in accordance with the research design and the smooth conduct of experiments.
Volume 31,2023 Issue 6
Volume 31,2023 Issue 6
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Effects of bear bile powder on promotion stage of early hepatocarcinogenesis in SD rats
dongrui, zhangmei, hongzexuan, tangqian, zouxinyu, jiaguiyang, niyuanping, Shibutani Makoto, jinmeilan
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Objective Bear bile powder (BBP), a natural Traditional Chinese medicine (TCM), has antioxidant and anticancer effects. To clarify the modification effect of bear bile powder (BBP) on early period of hepatocarcinoma formation, we conducted an anticancer efficacy experiment using short-term carcinogenesis bioassay models. Method Forty 5-week-old male SD rats were divided randomly into the following 4 groups with 10 animals per group: DEN alone, DEN+PBO, DEN+PBO+BBP-L (200mg/kg BBP), DEN+PBO+BBP-H (400mg/kg BBP). All rats were injected intraperitoneally with 200 mg/kg N-diethylnitrosamine (DEN) and three groups given a diet containing 0.5% piperonyl butoxide (PBO). In addition, the rats of last two groups were orally administered 200 or 400 mg/kg BBP for 8 weeks. Results The relative and absolute liver weights in PBO-treated groups significantly increased compared to DEN alone group. However, the number and area of GST-P+ foci were significantly decreased in only DEN+PBO+BBP-L group compared to DEN+PBO group. In addition, the Ki-67+ cell ratio which are significantly increased by DEN and PBO were significantly decreased after treatment with BBP in both BBP-treated groups. Interestingly, the mRNA levels of Ccne1, Cdkn1b related to cell cycle Caspase 8 and Caspase 9 related to apoptosis were significantly increased only in the BBP-H group. However, these changes were not observed in the BBP-L group. Conclusion These results indicated that BBP has a suppressive effect in the early period of hepatocarcinoma formation, leading to the inhibition of preneoplastic lesions. In addition, these results suggested that the suppression mechanism of BBP is strongly involved in the inhibition of cell proliferation activity and induction of apoptosis. Furthermore, that a high dose of BBP may influence BBP’s inhibitory effect on the preneoplastic lesions.
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The welfare and untilization of experimental animals in tumor research
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As an important intermediate link between in vitro cell experiments and clinical experiments, animal models are often preferred in the research of tumor mechanisms, prevention,diagnosis, and treatment. The results of animal experiments are directly related to animal welfare, and are important factors affecting the scientific and accurate results of the research. This article summarizes the relevant aspects of experimental animals involved in tumor research, including tumor animal models, animal welfare related to tumor models and humane endpoints.
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Progress in the study of animal models of systemic juvenile idiopathic arthritis and macrophage activation syndrome
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Systemic juvenile idiopathic arthritis (sJIA) is the most frequent rheumatic disease complicated by macrophage activation syndrome (MAS), which can be life-threatening in children. Current experimental animal models show only some of the characteristics of sJIA and MAS, and there is no perfect animal model that can replicate the whole process of sJIA and MAS. This article reviews the clinical features, advantages and shortcomings of these models, with the aim of providing ideas for exploring more representative animal models of sJIA and MAS.
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Quantitative inhalation method to established the model of chronic obstructive pulmonary disease in rats
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Objective To compare the differences of chronic obstructive pulmonary disease (COPD) models induced by smoke inhalation through nose-mouth plus LPS or smoke exposure through wholebody plus LPS in rats, providing a new model for COPD model construction. Methods 90 male SD rats were randomly divided into normal control group, wholebody exposure group and nose-mouth inhalation group, with 30 rats/group. The wholebody exposure group were exposed in a homemade smoke box where smoke contacted with whole body of rats , and the smoke nose-mouth inhalation group were inhaled with somke via nose-mouth only in a "quantitative smoking device". Animals in both groups were exposed to smoke once a day for 60mins/time for 8 weeks, and LPS (1mg/kg) was injected through the trachea on day 1, 7, 15 and 21, respectively, to induce the COPD model. The quality control of smoke generated by quantitative smoking devices included the verification of the stability and uniformity of the concentration of smoke particles and the size distribution of smoke particles. At 4, 6 and 8 weeks of modeling period, pulmonary function examination, the content of inflammatory factor interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in alveolar lavage fluid and histopathological examination were performed to compare the differences between the two modeling methods. Results Quantitative smoking devices could produce smoke with stable concentrations of 1.1mg/L (counted as total particles) and 0.1mg/L (counted as nicotine), respectively, with a median mass particle size of 0.693μm (in nicotine) and a GSD of 1.463. Compared with the whole body exposure group, the indexes of pulmonary function FEV0.2/FVC and pulmonary compliance (Cdyn) in the nose-mouth inhalation group decreased more significantly, and the airway resistance (Penh) increased more significantly. The levels of IL-6 and TNF-α in the alveolar lavage fluid of rats in the nose-mouth inhalation group were significantly increased at 6 weeks after modeling, while those indexs in the wholebody exposure group were increased at 8 weeks after modeling. The lesion severity of bronchial inflammation after modeling was similar between the oral-nasal inhalation group and the wholebody exposure group, but the lesion severity of emphysema was more serious in the oral-nasal inhalation group (the time when appeared statistic difference: oral-nasal inhalation vs. wholebody exposure = 6 weeks of modeling vs. 8 weeks of modeling). The mean linear intercept (MLI) in the oral-nasal inhalation group increased significantly at 4-8 weeks of modeling, and the mean alveolar numbers (MAN) decreased significantly at 6-8 weeks of modeling. MLI increased significantly and MAN decreased significantly in the whole body exposure group after 8 weeks of modeling. In the oral-nasal inhalation group, significant abnormal changes were observed in pulmonary function indexes (FEV0.2/FVC, Cdyn, Penh), cytokine levels in Bronchoalveolar lavage fluid (IL-6, TNF-α), and alveolar histopathological changes (bronchial severity and emphysema pathological score, MLI, MAN) after modeling. However, the coefficient of variation (CV%) of each index was significantly lower than that of the whole body exposure group. Conclusion LPS (1mg/kg) endotracheal drip combined with smoke wholebody exposured or via oral-nasal inhalation both could establish a typical rat COPD model. Rats Inhalated smoke via oral-nasal could shorten the modeling period. The model could be completed after 6 weeks of continuous modeling, presenting typical symptoms of chronic obstructive pulmonary disease (pulmonary ventilation dysfunction, broncho-lung chronic inflammatory infiltration, accompanied by emphysema), and the difference between individual model animals were smaller (vs smoke exposure, CV% values were smaller).
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Research progress of animal metacognition
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It is widely believed that metacognition is a special cognitive capacity that only humans possess. A contentious debate in the field of comparative psychology is whether animals have metacognition. The exploration of this question has become an important way to uncover the phylogenetic roots of metacognition and to map the evolutionary history of higher cognitive functions in humans. This paper reviewed the main animal metacognition studies in the past 25 years. We summarize three common research paradigms and corresponding measures: the uncertainty monitoring paradigm, the information seeking paradigm, and the confidence judgment paradigm. Two opposing explanatory tendencies and their rationales are outlined in the field of animal metacognition research: the associative model and the metacognitive model. In response to the debate between the associative model and the metacognitive model, two future research orientations are proposed to improve the research paradigm to test the metacognitive model and the innovation theory to integrate the model.
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Data mining based animal model for dilated cardiomyopathy
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Objective To review the animal species, modelling methods and evaluation indexes of dilated cardiomyopathy (DCM) animal models at home and abroad, to provide suggestions for improving the success rate of modelling and establishing DCM animal models with Chinese medicine characteristics in the future, and to provide reference for the establishment of future DCM animal models. Methods The literature on animal models of dilated cardiomyopathy in the past 10 years was searched, and relevant reports were collected and summarized. Relevant parameters of experimental animals (species, sex, body weight, etc.), modelling methods, modelling cycles, positive control drug species and cycles, and model evaluation indexes were summarized and analysed. Results A total of 128 papers were included. Animal models of dilated cardiomyopathy were mostly prepared in SD rats and Wistar rats using the anthracycline adriamycin, with a cycle of 30 d
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Study on the expression and methylation level of hippocampal Notch signaling pathway genes in perimenopausal depression rats
shen jian ying, liang wen na, chen hui fang, zhang ling yuan, zhuang yuan ying, chen xiao yang, chen ya ru, xiao qiong qiong, yang min, gong lin, min li
Abstract:
[Abstract] Objective To investigate the effect of perimenopausal depression on the expression of key genes of Notch signaling pathway and DNA methylation of its promoter in rat hippocampus from the perspective of DNA methylation of epigenetics. Methods 12-month-old female SD rats were randomly divided into control group and model group. Open field tests, sugar consumption tests, and forced swimming tests were used for behavioral evaluation. Real-time PCR was used to detect the expression of key genes of Notch signaling pathway in the hippocampal dentate gyrus of different groups. Bisulfite sequencing (BSP) was used to analyze methylation sites and methylation levels in the promoter region of key genes of the Notch signaling pathway. Results In perimenopausal depression rats, the horizontal and vertical scores of open field test and the rate of sugar water consumption decreased significantly; the expression of the key genes Jagged1, Notch1 and Hes5 on Notch signaling pathway was significantly down regulated in the hippocampus of perimenopausal depression rats (P＜0.01 or P＜0.05) ; among them, some methylation sites and methylation rates of Hes5 gene increased significantly, while the methylation sites and methylation rates of Jagged1 and Notch1 genes were not statistically significant (P>0.05) . Conclusion The expression of key genes of Notch1 signaling pathway in the hippocampal dentate gyrus of perimenopausal depression rats is significantly down regulated, and the down-regulation of Hes5 gene may be related to the increase of promoter DNA methylation level.
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Establishment and evaluation of rats model of rheumatoid arthritis with depression
liyuanyuan, zhangbitao, fanpeijian, cuizilong, wangshaoxian
Abstract:
Objective To prepare and evaluate the animal model of rheumatoid arthritis with depression (RAD). Methods Thirty-two rats were randomly divided into normal group (N group), depression group (D group), arthritis group (RA group) and model group (RAD group), with 8 rats in each group. The N group was fed normally, while the D group was fed solitary rearing for 1 week and chronic unpredictable mild stress (CUMS) for 3 weeks, RA group was induced by collagen-induced arthritis (CIA) to establish the arthritis model. In RAD group, RAD animal model was established on the basis of CIA animal model, meanwhile, adding 1 week solitary rearing and 3 weeks CUMS. Toe volume, arthrits index (AI), Synovial and ankle joint pathology, serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were used to evaluate whether the rat model of rheumatoid arthritis was successfully established; the depression status of rats was evaluated by measuring body weight, food intake, sugar water preference rate, open field behavior (total number of motion cells, number of standing uprights), serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), and pathological changes of hippocampus. The RAD animal model was successfully prepared if depression and rheumatoid arthritis were both tested in the rats. Results Compared with the N group, toe volume, AI score and the levels of IL-1β, IL-6 in serum of RA group and RAD group were significantly increased (P＜0.05 or P＜0.01), the joint space widened, synovial hyperplasia was obvious and extended to the joint cavity, and a large number of inflammatory cells were seen; in D group and RAD group, body weight, food intake, total number of motion cells, number of standing uprights and sugar water preference rate of rats were decreased to different degrees, and the levels of CRH, ACTH, CORT in serum were increased in different degrees (P＜0.05 or P＜0.01), the neuron cells arranged loosely, gap increased, the number decreased, accompanied by some nucleus pyknosis, dissolution, rupture, especially in the model group. Conclusion CIA combined with solitary rearing and CUMS can better simulate the changes in the external manifestations and internal indicators of RAD model animals, which can provide reference for the study of RAD disease animal models.
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Research hotspots and trends of Alzheimer's disease animal experiments: CiteSpace bibliometric analysis based on WOS database
YANG Jia-hui, LIN Yin, CHEN Lai, luoxiaoquan
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Objective Alzheimer's disease (AD) brings a huge burden to patients and society. As an important means of studying AD, animal experiments provide a lot of scientific basis for clinical and scientific researchers. This paper adopts the method of bibliometric analysis to reveal the research status, hotspots and trends in the field of AD animal experiments. Methods We obtained publications in the field of AD animal experiments from 2018 to 2022 from the Web of Science Core Collection (WoSCC) database. We use the analysis software CiteSpace 6.2.R2 (Advanced) to analyze the general information and keywords of publications in this field. Results After analyzing 4015 articles included in this study from 2018 to 2022, it was found that the annual publication volume of papers has gradually increased. In terms of the number of articles, the United States, the University of California System, Saito T, and the International Journal of Molecular Science are the countries, institutions, authors, and journals with the largest number of articles. "Alzheimer's disease" had the highest frequency of occurrence, and "anxiety" had the highest central degree. Conclusion This field focuses on the study of pathogenesis and treatment methods, and the plasticity of entorhinal cortex, neurons and synapses is a hotspot of current research. Future research trends may mainly focus on Aβ plaque formation, tau hyperphosphorylation, neurofibrillary tangle accumulation, glial inflammation, and ultimately loss of proper neuroplasticity. This article visually analyzes the hotspots and trends of AD animal experiments to help researchers understand the latest situation.
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Plantar injection of complete Freund's adjuvant induced behavioral and monoamine neurotransmitter changes in pain and depression comorbid model rats
Abstract:
Objective To observe the effects of plantar injection of complete Freund's adjuvant (CFA) on pain-depressive behavior and changes in hippocampal monoamine neurotransmitters in rats, with the aim of establishing an animal model of related comorbidity. Methods 16 male, 8-week-old, SPF-grade healthy SD rats were randomly divided into a model group and control group with 8 rats in each group. In the model group, rats were anesthetized and injected with 100 μL of CFA in the left hind paw to induce the comorbid pain and depression model. In the control group, rats were injected with the same volume of saline. Pain thresholds were measured using the von Frey hair and thermal radiation instrument, and depressive-like behaviors were assessed using open field test (OFT), tail suspension test (TST), and forced swim test (FST). Enzyme-linked immunosorbent assay (ELISA) was used to measure the content of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in the rat hippocampal tissue, and histological changes in the hippocampal area were observed by hematoxylin-eosin (HE) staining. Results Compared with the control group, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in the model group were significantly decreased at 3, 7, and 14 days (P < 0.01); the total distance in the OFT was significantly reduced at 7 and 14 days (P < 0.01), and the time spent in the center zone was significantly decreased at 14 days (P < 0.01); the immobility time in the TST was significantly increased at 14 days (P < 0.01), and the immobility time in the FST was significantly increased at 7 and 14 days (P < 0.05, P < 0.01); the content of 5-HT, DA, and NE in the hippocampal tissue of the model group rats was significantly reduced compared with the control group (P < 0.01), and the hippocampal tissue in the model group showed pathological changes, including irregular neuronal shapes, loose and disordered arrangement, increased intercellular space, some unclear cell nuclei, and some neuronal contraction and apoptosis. Conclusion Injection of 100 μL of CFA in the footpad can cause pain hypersensitivity, depressive-like behavior, significant reduction of monoaminergic neurotransmitters in the hippocampus, and histological changes in the hippocampus, effectively simulating the manifestations of comorbid pain and depression, and is an experimental model for studying the pathological mechanisms of comorbid pain and depression.
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Research Progress of Neurotransmitter Detection Technology in Living Brain
Zhu Mingyu, Cui Lili, Chen Huan, Hou Hongwei, HU Qingyuan
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As an endogenous chemical substance, neurotransmitter plays a vital role in maintaining normal life activities of people. Abnormal levels of neurotransmitters can lead to physical, mental and some neurodegenerative diseases. However, the ultra-low concentration, complex chemical properties and release modes of neurotransmitters make their accurate detection in vivo a great challenge.In order to accurately monitor neurotransmitters in the brain and accurately understand the release kinetics of neurotransmitters, several commonly used methods for detecting neurotransmitters in vivo in the past five years and their research progress were reviewed.The basic principle and applicability of microdialysis, electrochemical sensor and fluorescence sensor are introduced in detail.
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Research progress on animal models of acute exacerbation of various respiratory diseases induced by compound factors
Qiu Zhiguang, SHAO Xuejie, LU Ruilong, TAN Yange, REN Zhouxin
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Based on the compound factors of clinical practice, some progress has been made in acute exacerbation models of respiratory diseases by "two-hit" method. In this review, the current research on acute exacerbation models of pulmonary fibrosis, chronic obstructive pulmonary disease and bronchial asthma constructed by compound factors is summarized. Furthermore, the characteristics and scope of application of each model are compared and analyzed in animal strain selection, model preparation methods and major histopathological changes, providing reference for researchers to further improve and perfect the model or rationally select the animal models.
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Effect of miR-185-5p on proliferation, invasion and migration of mouse breast cancer PY8119 cells
Liu Lu, Zhao Yanqiao, Wang Xiaona, Wang Kun, Yin Chonggao, Liu Qinghua, Li Hongli
Abstract:
Object To investigate the effect of miR-185-5p on the proliferation, invasion and migration of mouse breast cancer PY8119 cells. Methods Mirna: miR-185-5p with significantly down-regulated expression in breast cancer was obtained by previous research group. The sequence of miR-185-5p gene from human and mouse was consistent by NCBI. The effects of overexpression and knockdown of miR-185-5p on the proliferation of PY8119 cells were detected by EdU proliferation experiment. The effects of overexpression and knockdown of miR-185-5p on the invasion ability of PY8119 cells were detected by Transwell invasion experiment. The effects of overexpression and knockdown of miR-185-5p on the migration ability of PY8119 cells were detected by scratch healing experiment. The effects of overexpression and knockdown of miR-185-5p on the apoptosis of PY8119 cells were detected by flow cytometry. The effect of overexpression of miR-185-5p on tumor proliferation in vivo was detected by C57BL/6 mouse subcutaneous tumor model. Lung metastasis of mice overexpressing miR-185-5p was observed by tail vein injection. Results The results of EdU proliferation experiment, Transwell invasion experiment, scratch healing experiment and flow cytometry showed that knocking down miR-185-5p significantly enhanced the proliferation, invasion and migration of PY8119 cells and inhibited apoptosis. Overexpression of miR-185-5p inhibited the proliferation, invasion and migration of PY8119 cells and promoted apoptosis. In vivo tumorigenesis experiment of C57BL/6 mice showed that overexpression of miR-185-5p slowed down the tumor growth rate in C57BL/6 mice. Lung metastasis experiment showed that overexpression of miR-185-5p inhibited the lung metastasis of C57BL/6 mice. Conclusion miR-185-5p can inhibit the proliferation, invasion and migration of mouse breast cancer PY8119 cells in vitro and in vivo as a tumor suppressor gene.
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To investigate the effect of TMAO on lipid metabolism in spleen deficiency hyperlipemia rats and the intervention effect of Xiangsha Liujunzi decoction
Abstract:
Objective To investigate the effect of TMAO, a metabolite of intestinal flora, on hepatic lipid metabolism in rats with splenic deficiency and hyperlipidemia, and to further explore the possible mechanism of Xiangsha Liujunzi Decoction in the intervention of hepatic lipid metabolism disorder. Methods SD rats were divided into: (1) Blank control group (group C), (2) blank control group DMB (group C D), DMB is TMAO inhibitor, (3) spleen deficiency hyperlipidemia group (PG group), (4) spleen deficiency hyperlipidemia DMB group (PG D), (5) Spleen deficiency hyperlipidemia Xiangsha Liujunzi Decoction group (PG XS group), Except group C and group C D, the other groups were constructed to establish spleen deficiency hyperlipidemia model (12 weeks of modeling) by combining excessive fatigue and high-fat diet. After model establishment, group C D and PG D were given 1%DMB in drinking water every day, and group PG XS was given Xiangsha Liujunzi decoction (11.34 g crude drug /kg/ day) every day. The other groups were given the same amount of normal saline. The blood lipid level of each group was detected by automatic biochemical method after 4 weeks of intragastric administration. The morphological changes of liver were observed by HE staining. The lipid deposition in the liver of each group was observed by oil red O method. Liver FFA, TG and TC were detected by ELISA. The plasma TMAO content was detected by LC-MS. The relative expression levels of PERK, FOXO1, SREBP-2, ABCA1 and miR-33 mRNA in liver were detected by qRT-PCR. The contents of SREBP-2 and ABCA1 gene protein in liver were detected by WB. Results (1) The content of TC, TG and LDL-C in serum of PG group was significantly higher than that in C group, and the content of HDL-C was significantly lower than that in C group; The contents of FFA, TG and TC in liver tissue of PG rats were significantly increased compared with those of C group. Compared with group C, lipid deposition in liver was aggravated and fat vacuoles were increased significantly. There was no difference between group C D and group C in the above indexes. Compared with the PG group, PG D and PG XS groups could significantly reduce the contents of TC, TG and LDL-C in serum, increase the content of HDL-C, reduce the contents of FFA, TG and TC in liver tissue, alleviate the phenomenon of lipid deposition in liver tissue and reduce liver vacuoles. There was no significant difference between PG D group and PG XS group. (2) Compared with group C, the plasma TMAO content of PG group was significantly increased, the liver PERK, FOXO1 and miR-33a mRNA expressions were significantly increased, and the liver SREBP-2 and ABCA1 mRNA and protein expressions were significantly decreased; There was no difference between group C D and group C in the above indexes. Compared with the PG group, PG D and PG XS groups could significantly reduce the plasma TMAO content, decrease the liver PERK, FOXO1 and miR-33a mRNA expressions, and increase the liver SREBP-2 and ABCA1 mRNA and protein expressions. There was no significant difference between PG D group and PG XS group. Conclusion TMAO may regulate the SREBP-2/miR-33a/ABCA1 signaling pathway through PERK/FOXO1 axis to cause liver lipid metabolism disorders in rats, and Xiangsha Liujunzi Decoction may inhibit liver lipid metabolism disorders by inhibiting TMAO content.
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Study on the effect of Huanglian Jiedu Decoction on bile acid metabolism in SD rats based on serum metabolomics
yangguangyong, duhaiyang, zhanggengxin, sugang, tuxiaohua, heguangzhi
Abstract:
Objective To study the effect of Huanglian Jiedu Decoction(HLJD) on the physiological function of healthy SD rats through serum non-targeted metabolomics. Methods After 7 days of adaptive feeding, 24 rats were randomly divided into blank group (group N) and high-dose HLJD group (group H), medium-dose HLJD group (group M), and low-dose HLJD group (group L) with six rats per group. Group N was gavaged with physiological saline, and H, M, and L groups were gavaged with 6.250, 3.125, and 1.560 g/kg HLJD, respectively. Rats were gavaged with 1 mL twice per day for 21 d. Before collecting serum samples, fasting and water deprivation were performed for 12 h. After anesthesia, blood was collected from the abdominal aorta, and serum was separated. Changes in metabolic products in the serum were detected by Gas Chromatography Time-of-Flight Mass Spectrometry(GC-TOF-MS). Multivariate analysis by Orthogonal Projections to Latent Structures Discriminant Analysis(OPLS-DA) and univariate statistical methods were used to screen differential metabolites, and then metabolic pathway analysis was conducted using the Metabo Analyst platform. Results Compared with the group N, metabolic small molecules were significantly altered in the serum of group H, group M, and group L, which mainly included cholesterol, cholic acid, ribose, paclitaxel, cortisol, oleic acid, succinic acid, linolenic acid, acetic acid, and acetone alcohol (P < 0.05). Correlation analysis showed that HLJD significantly affected the metabolism of primary bile acids, alanine, aspartic acid, and glutamate in α-linolenic acid and glycerol phospholipid metabolism, and its in vivo effects may be related to the intake dose, providing a reference to further reveal the mechanism of HLJD in promoting bile acid metabolism. Conclusions HLJD promotes the production of primary bile acids in vivo and enhances the effects of the bile acid metabolic pathway.
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The model of ulcerative colitis with spleen deficiency and dampness syndrome and the changes of T lymphocytes
qiuping xiao, zhong youbao, yu songren, li shangshang, luo xiaoquan, chen liling, liu xuan
Abstract:
Objective A mouse model of ulcerative colitis with spleen deficiency and dampness syndrome was established, and the role of T lymphocytes in this model was studied. Methods C57BL/6 mice were randomly divided equally into Control, FXY, 3% DSS, FXY+3% DSS and FXY+2% DSS groups. A mouse model of ulcerative colitis with spleen deficiency and dampness syndrome was established by DSS and senna leaf. At the end of moulding, HE staining was performed to observe structural changes in the colon tissue. Elisa assay was performed to detect the concentrations of inflammatory cytokines in the colon tissues. Flow cytometry was used to detect the levels of CD4/CD8 T lymphocytes, Th1/Th2, Th17/Treg cells. Results In the FXY group, the clinical symptoms of mice with spleen deficiency and dampness were mainly diarrhea, and mice with 3% DSS colitis mostly showed blood in stool, while mice with spleen deficiency and dampness colitis in the FXY+3%DSS and FXY+2%DSS groups mostly showed diarrhea and blood in stool, but the survival rate of mice in the FXY+3%DSS group was as low as 50%. Compared with the Control group, body weight, colon length and concentrations of anti-inflammatory cytokines IL-10 and TGF-β1 were significantly lower in the 3%DSS, FXY+3%DSS and FXY+2%DSS groups, while concentrations of DAI, colon weight, colon weight index, colon weight/colon length, pro-inflammatory cytokines TNF-ɑ, IL-1β and IL-6 were significantly increased, and significant ulcer formation and inflammatory cell infiltration were observed under light microscopy. Compared with the Control group, the percentages of CD4, Th1 and Th17 cells in the mesenteric lymph nodes of FXY+3% DSS and FXY+2% DSS groups were significantly increased, while CD8, Th2 and Treg cells were significantly decreased. Conclusion The combination of Senna and 2% DSS could successfully construct a model of mice with ulcerative colitis with spleen deficiency and dampness evidence, showing typical CD4/CD8, Th1/Th2 and Th17/Treg cell imbalance characteristics.
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Progress in the application of the zebrafish model in the study of neurodegenerative diseases
Abstract:
【Abstract】 With the process of the aging society, the incidence rate of neurodegenerative diseases is increasing year by year. Zebrafish have many advantages that other model organisms do not have, such as unique growth and development mode, low price and easy reproduction, and highly similar to human genes. In the past decades, zebrafish as a model organism has been widely used in various research fields of medicine and life science. This article reviews the application and progress of zebrafish in the research of several common neurodegenerative diseases in recent years, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, hereditary spastic paraplegia, and other diseases related to the nervous system. This review article analyzes and summarizes the advantages and disadvantages of zebrafish as an ideal model organism. In future research, especially in the mechanism research of neurodegenerative diseases and large-scale screening of therapeutic drugs, zebrafish has considerable application prospects.
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Research progress on animal model construction and evaluation of different TCM syndromes of gastric ulcer
Wang Wen, Hou Yujun, Wang Lu, Yan Xiangyun, Li Yanqiu, Sun Luqiang, Chen Shuai, Shi Yinzhou, Zheng Qianhua, Li Ying
Abstract:
Gastric ulcer is a common digestive system disease. Traditional Chinese medicine (TCM) has a significant effect in treatment of this disease. However, its treatment mechanism is unclear. Establishing a scientific and objective animal model and model evaluation system is of great significance to promote development of TCM in this field. This article organizes the literature related to treatment of gastric ulcer by TCM in the past 10 years and summarizes methods for establishing and evaluating animal models of TCM syndromes relating to gastric ulcer. The methods were reviewed for liver and stomach disharmony syndrome, spleen and stomach dampness-heat syndrome, blood stasis in stomach syndrome, deficiency cold of spleen and stomach syndrome, stomach Yin deficiency syndrome, and liver depression and spleen deficiency syndrome. The current animal models of gastric ulcer had the following problems: the typing of TCM syndromes was not unified, the methods and syndrome types of the models were limited, the standards of model establishment methods were different, the combination of disease and syndrome of models was not close enough, and the model evaluation system was not standardized. Suggestions for model improvement are proposed to provide a reference for research in this field.
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Analysis of pathological changes of knee joint and intestinal tissue in cynotonic spondylitis monkeys
huangyuye, caiyanzhen, caichunmei, zhuhepeng, dinghuangguan, xiaowende, chenjun, luli
Abstract:
Objective: Ankylosing spondylitis (AS) is an immune-mediated chronic disease involving axial joints, peripheral joints and intestines, but the etiology of peripheral knee and intestine has been unknown. This study aimed to study the main pathological changes and mechanisms of knee joint and intestine in cynomolgus monkeys with AS. Methods: Through histomorphological analysis and immunohistochemical experiments, the key characteristics of peripheral knee joint and intestinal tissues of AS were studied and the possible pathogenesis was preliminarily analyzed. Results: The pathological characteristics of peripheral knee joints in AS cynomolgus monkeys mainly showed cartilage erosion on the joint surface, exposed subchondral bone, and jagged joint surface in the early stage. In the late stage, it is mainly manifested as ectopic hyperplasia of cartilage superficial hypertrophy of chondrocytes, and osteophytes are formed through chondroplaginous osteogenesis and fibroogenesis, and cartilage is basically lost. The expression of MMP-3 in cartilage and blood vessels is upregulated, causing cartilage destruction and stimulating angiogenesis. AS cynomolgus monkeys have severe atrophy of small intestinal villi and obvious crypt hyperplasia, and a large number of γδ T cells can be seen in the mucosal intestinal glands of the jejunum and ileum. Conclusion: In this study, the pathological analysis of knee joint and intestine of AS cynomolgus monkey obtained the key characteristics of knee joint and intestinal tissue of this spontaneous model, and proposed a possible pathogenesis. This paper provides new insights into the potential link between autoimmunity in bone tissue and intestinal tissue lesions in AS.
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Langendorff Cardiac Perfusion Technique (for Myocardial Ischemia Reperfusion) applications and developments
Linan, Zhang Chen, Sun yanjun, Gao Shengwei, Li Duojing, Wang xinrui, Wang Baohe
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The Langendorff ex vivo cardiac perfusion model technique is reproducible, easy to administer and has low technical requirements, and is often used to study myocardial ischemia-reperfusion injury diseases. This article reviews the steps of this technique, selection of animals, perfusion patterns, selection of perfusate, indices of detection, ischemic modalities, and selection of ischemia and perfusion times.
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Study on the antidiarrheal effect of new "Ershen pills", a composition of new sliced nutmeg Koji
Abstract:
Objective To evaluate the antidiarrheal effect of new ershen pills composed of nutmeg koji instead of bran stewed nutmeg.Method Kunming mice were randomly divided into normal group, model group, Ershen pills Ⅰ (salt psoralen + bran stewed nutmeg), Ershen pills Ⅱ (salt psoralen + nutmeg koji), Ershen pills Ⅲ (salt psoralen + nutmeg raw product), salt psoralen group, and nutmeg koji group. The combined modeling method of "hydrocortisone + senna leaf" was used to establish the diarrhea mouse model with spleen-kidney Yang deficiency. The general signs and pathological changes of each organ were observed. The levels of various organs index, small intestine propulsion rate, gastric residual rate, serum motilin (MTL), gastrin (GAS), adrenal ketone (CORT), thyroid stimulating hormone (TSH), testosterone (T), tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) were detected. 16S rDNA sequencing and information analysis were conducted for fecal microorganisms. Results After modeling, compared with normal group, the weight and activity of mice in model group were reduced, small intestine propulsion rate was significantly increased, gastric residual rate and organ index were significantly decreased, serum GAS, CORT, TSH and T levels were significantly decreased, MTL, TNF-α and IL-β levels were significantly increased, and intestinal flora species diversity was decreased. After administration, the above indexes and symptoms were improved in different degrees in each administration group, and Ershen Pills group Ⅱ was better than Ershen Pills group Ⅰ, Ershen Pills group Ⅲ, salt-psoralea and myristoqu groups. Conclusion The combined use of nutmeg koji and salt psoralen has a remarkable effect on the diarrhea of spleen and kidney Yang deficiency. The fermented nutmeg can reduce its toxic risk and enhance its effect of warming spleen and preventing diarrhea, which laid a foundation for the development of nutmeg koji.
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Characteristics and application analysis of ovarian cancer animal model
yi chu, zhan sha, ma xin yi, wu yang jie, bu jun yi, ma min, yan xian xin
Abstract:
【Abstract】Objective To study the characteristics and application status of animal models of ovarian cancer and provide guidance for standardized preparation of ovarian cancer models. Methods Using “ovarian cancer” and “animal model” as the main topics in CNKI, Wanfang, VIP, and PubMed databases, the databases were searched for animal experimentation literature on ovarian cancer from establishment of the database to March 1, 2023. A total of 1428 relevant articles were collected. From the experimental animal species, age, experimental modeling methods, detection indicators, and other aspects of the summary, we established a database for systematic analysis. Results A total of 178 studies were obtained after screening. Female BALB/c mice were selected to establish the animal model of ovarian cancer. Most choices were 4 ~ 6 and 6 ~ 8 weeks of age. The most common modeling method was ectopic transplantation, which was mostly subcutaneous injection in the axilla. In terms of modeling methods of ovarian cancer in animals, transplantable models were the most used, and ectopic transplantation was more often employed than orthotopic transplantation. The ovarian cancer cell lines used were mostly human. Most detection indexes were the appearance of tumor tissue, tumor pathology, and immunohistochemistry. Conclusion Animal models of ovarian cancer are widely used in ovarian cancer research, but standard preparation and evaluations are lacking. We analyzed the application status of animal models of ovarian cancer in detail through literature collation and data classification analysis to provide a reference to establish standardized animal models of ovarian cancer. BALB/c mice are the most selected, and human ovarian cancer cell line SKOV3 at 1 × 107 cells/ml is commonly injected into the subcutaneous axillary area for 10 days. A large number of models can be obtained in a short time with a high tumor formation rate and small individual differences, which provide a reference to study ovarian cancer.
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Model establishment and evaluation of rats with chronic obstructive pulmonary disease complicated with chronic kidney disease
Fanzhengyuan, Li Ya, LI Suyun, LI Gaofeng, LI Jingmei
Abstract:
Objective To establish and evaluate a model of chronic obstructive pulmonary disease (COPD) combined with chronic kidney disease (CKD) in rats. Methods Forty SPF grade SD rats were randomly divided into control, COPD, CKD, and COPD combined with CKD model (COPD+CKD) groups, with 10 rats in each group. The COPD rat model was prepared by cigarette smoke exposure combined with the bacterial drip method, the CKD rat model was established by adenine induction, and the COPD combined with CKD rat model was prepared by both methods. Results After successful modeling, lung function indexes incluidng forced vital capacity (FVC), forced expiratory volume in 0.1s (FEV0.1), and FEV0.1/FVC were significantly reduced in the COPD+CKD group (P < 0.01), and lung histopathology showed emphysematous changes with alveolar wall fracture and fusion as well as inflammatory cell infiltration. Serum Cr, BUN, and 24 h urine protein were significantly increased (P < 0.01). Renal histopathology showed glomerular mesentery proliferation, basement membrane thickening, tubular dilatation, and interstitial fibrosis. The ultrastructure showed that glomerular capillary loops were partially closed, foot processes were fused, renal tubule mitochondria were fused and disintegrated, and lysosome was increased. Serum IL-6, IL-13, IL-1β, and TGF-β1 levels were significantly increased (P < 0.01) and were significantly higher than those in single model groups (P < 0.01). Conclusions Cigarette smoke exposure combined with bacterial infection and 2.5% adenine induction successfully establishes a model of COPD complicated with CKD in rats, and the inflammatory response might play a major role in the process of COPD complicated with CKD.
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Research progress of functional dyspepsia animal model based on the combination of disease and syndrome
liuhao, wangxinai, liwenjing, wuyaxuan, wangchenqi, xiaohongling
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Functional dyspepsia (FD) is a non-organic disease mainly due to regional dysfunction of stomach and duodenum. In traditional Chinese medicine(TCM), it is classified as "epigastric fullness" and "epigastric pain", and divided into the syndrome types of spleen deficiency and qi stagnation, spleen-stomach deficiency-cold(weak), spleen-stomach damp-heat, liver-stomach disharmony, and cold- heat complicated. TCM has a significant effect and high acceptance in the treatment of FD, and the animal model with the combination of disease and syndrome is the basis and prerequisite for relevant research. Therefore, this paper organized and summarized the existing research on animal models of FD combined with disease and syndrome, explored the reasons for the selection of specific modeling methods and evaluation indicators, and proposed the shortcomings of the current research, in order to provide support for the future research on animal models of FD combined with disease and syndrome.
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Collagen peptide combined with sodium alginate improved intrauterine adhesions in mice by down-regulating the expression of NLRP3 inflammasome
chengyiyi, zhaoweiwei, song zhenfeng, tongfuwen, liugang, zhanghua, shileilei, guozhikun, wangxianwei, panying, sunyongkun
Abstract:
【Abstract】Objective To investigate the repair effect and mechanism of collagen peptides (CP) combined with sodium alginate (SA) on endometrial injury. Methods Forty-eight SPF female C57BL/6N mice were randomly divided into sham group (16 mice), model group (16 mice) and CP SA group (16 mice). In the model group, 95% ethanol was injected into the uterine cavity through the cervix to induce endometrial injury, and the intrauterine adhesion model was established. The sham operation group was injected with 0.9% normal saline into the uterine cavity. The treatment group was injected with the mixture of CP SA after the injection of 95% ethanol into the uterine cavity. After 7 days of modeling, 8 mice in each group were selected to collect samples for each test. HE staining was used to observe the pathological changes of mouse uterine tissue. Modified Masson tri-color staining was used to observe endometrial fibrosis. Western blot was used to detect the protein expression levels of inflammatory factors NLRP3, ASC, Caspase-1, IL-1β and IL-18 in uterine tissues. ELISA was used to detect the expression of IL-1β and IL-18 in serum. The remaining 8 mice in each group were cohoused according to the male-female ratio of 1:2, and the number of pregnant mice in each group was recorded. Pregnant mice were euthanized in the 14th day of pregnancy, and the number of embryos was recorded. Results (1) Compared with the sham operation group, the model group showed thinner endometrial thickness, increased endometrial fibrosis, and inflammatory cell infiltration. In addition, the protein expression levels of inflammatory factors NLRP3, ASC, Caspase-1, IL-1β and IL-18 in uterine tissue and the levels of IL-1β and IL-18 in serum in the model group were significantly lower than those in the sham operation group (P<0.05). (2) Compared with the model group, the treatment group showed that the degree of endometrial injury, endometrial fibrosis and inflammatory cell infiltration were reduced. In addition, the protein expression levels of inflammatory factors NLRP3, ASC, Caspase-1, IL-1β and IL-18 in uterine tissue and the levels of IL-1β and IL-18 in serum in the model group were significantly decreased than those in the sham operation group (P< 0.05). (3) Compared with the sham group, the reproductive ability of the model group decreased (P<0.05). Compared with the model group, the reproductive ability of the treatment group was significantly improved(P<0.05). Conclusions The combined application of CP and SA can effectively improve the pathological changes of uterine tissue, reduce endometrial injury, inflammatory response and fibrosis, and improve the reproductive ability of mice. The mechanism may be related to the down-regulation of NLRP3 inflammasome expression, which provides a reliable experimental basis for the combined application of CP and SA in the treatment of intrauterine adhesion.
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Research progress of bronchoalveolar lavage in mice
Wu Zhihao, Yang Luyin, Ren Wei, Zhou Yanan, Wang Hong, LeiYun, Yu Hong, Yang Sijin
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Bronchoalveolar lavage is an important technique for studying respiratory diseases and has been widely used in disease research. Currently, the operation procedure of bronchoalveolar lavage in clinical patients has been gradually standardized, while mice, as one of the important model animals for studying lung diseases, still need a standard collection and testing procedure for bronchoalveolar lavage fluid for mice. An unstandardized procedure can hinder the promotion and application of this technique in research, and also affect the accuracy and reliability of experimental results. This paper presents a systematic summary of bronchoalveolar lavage methods for mice in domestic and international studies, with the aim of providing reference and guidance for researchers to apply and establish a standardized lavage procedure in the future.
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Advances in Animal model for studying albumin-related drugs
Ziyin, Ning Li, Tang Chengcheng, Zhou Xiaoqing
Abstract:
The main challenges of therapeutic peptides or proteins is their short plasma half-life. The drugs combining these peptides or proteins were defined as albumin-related drugs. Such combination can effectively prolong the plasma half-life. Animal model is an important and indispensable tool for studying drug pharmacokinetics. This review summarizes two main animal models; rodents (wild-type mice, gene-modified mouse models, rat models) and non-rodents (monkeys), and their development and application in albumin-related drugs. This review can provide a reference for further studies on albumin-related drugs.
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Research progress on the establishment of mouse atherosclerosis model by different intervention factors
baixufeng, cao qingyu, 胡, wang shuwen, liu yali
Abstract:
Atherosclerosis (AS) is a potential risk factor for common cardiovascular and cerebrovascular diseases. Prevention and treatment of AS and research and development of anti-AS drugs have been a focus in the field of medicine. Selection of the ideal AS animal model is important to study prevention and control measures of AS and to research and develop traditional Chinese medicine for AS. The ideal animal model of AS should have similar pathogenesis to human AS, consistent pathological and biochemical reactions, high repeatability, simple operation, and easy adoption. Mice have the characteristics of strong reproduction, high heritability, good plasticity, and fast modeling of AS, and they have become ideal animals for AS research. In this article, the replication methods of the mouse AS model established by various intervention factors were compared and analyzed to provide a reference and ideas for prevention and treatment of AS and research and development of traditional Chinese medicine for AS.
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Application and development of germ-free animals for the gut microbiome research
Hu Yaqian, Wang Shanshan, Zhang Tong, Yuan Jiali, 胡
Abstract:
In recent years, with the introduction of the concept of metagenomics, human metagenomics has also become a new approach to reveal the development and health of humankind. As the largest microflora in the human body, the gut microbiome has been found to play an important role in the normal physiological functions of the human body and the occurrence and development of diseases. The variety and quantity of gut microbiome are abundant. In the study of gut microbiome, the application of germ-free animals makes the experiment more accurate and convenient. It is an ideal basic animal model. Not only that, models developed on this basis are also of great significance to this type of research. This review summarizes the understanding of germ-free animals, the application of germ-free animals in experimental research and the prospects of germ-free animal models, to review the application and development of germ-free animals in the gut microbiome.
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2016,24(3):321-326, DOI: 10.3969/j.issn.1005-4847.2016.03.020
Abstract:
The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. Animal models of depression used as the main methods to study the pathogenesis mechanism and select effective drugs receive increasing concerns. Current popular models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology. In this context, this study aims to review the animal models of depression and pathogenesis related with face validity, construct validity, and predictive validity of these models. These models include stress-induced models, injury-induced models, drug-induced models and transgenic models which all mimic the depression symptoms of human to some degree and are of great value for developing new antidepressant drugs and studying the pathogenesis of this disease.
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WU Ya-qi, ZHONG Gen-shen, WU Min-na
2015,23(3):249-255, DOI: 10.3969/j.issn.1005-4847.2015.03.006
Abstract:
Objective To explore the objectivity and scientificity of fecal sampling, and to provide reference for investigating the relationship between intestinal microbes and diseases. Methods Terminal restriction fragment length polymorphism, degeneration gradient gel electrophoresis and real time fluorescent quantitative PCR techniques were applied to differentially analyze the bacterial community composition and abundance of intestinal contents and feces taken from different sites of BALB/c mouse intestine. Results The predominant T-RFLP fragments (T-RFs) in feces in the rectum and colon were 244 bp, 255 bp and 449 bp, however, those in feces of the small intestine including duodenum, jejunum and ileum were 60 bp, 73 bp, 261 bp, 268 bp and 272 bp, and with a larger variation of the bacterial community composition in various parts of the small intestine. The bacterial abundance in the contents of duodenum and jejunum were 6.9 log (copies)/g and 8.3 log (copies)/g, fewer than in the other parts of the intestine, while the bacterial abundance in the feces was as high as 11.8 log (copies)/g, being about 2 times higher than that in the duodenum and jejunum (P<0.05), and similar to that in the ileum and colon content (P>0.05). Conclusions The inter-mouse variations of bacterial community composition in the large intestine contents are small. The bacterial composition and abundance are similar suggest that studies on the relationship between large intestine especially colorectal microbiota and diseases may be conducted via fecal sampling.
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LIAO Hui-dan, LONG Ling-ling, YAN Jie
2015,23(4):410-414, DOI: 10.3969/j.issn.1005-4847.2015.04.015
Abstract:
Objective To compare three methods for culture of fetal cortical neurons of SD rats and find out the suitable culture conditions of fetal cortical neurons in vitro. Methods The cortex of 16-18-day embryonic rat was used for culture in this study. Mechanical dissociation, trypsin digestion and papain digestion were applied respectively to the neuron culture. The morphological characteristics of neuronal cells at different time points were observed and neuron purity was identified by immunofluorescence staining assay. Results High purity of the fetal rat cortical neurons was successfully achieved by all the three culture methods, and each had distinct morphological characteristics at different time points. The purity of neurons was 96.28%, 95.63% and 97.34%, respectively, with no significant differences among the three groups (P>0.05).Conclusions The three culture methods are improved in our study. Stable neurons with high purity can be obtained by all the three methods respectively, and each of these methods has distinct characteristics.
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MIAO Jinxin, SONG Shaohe, LI Xiumin
2020,28(2):0-0, DOI: 10. 3969 / j.issn.1005-4847. 2020. 02. 018
Abstract:
Colorectal cancer is one of the most common malignant tumors worldwide, and the morbidity and mortality rate is increasing year by year with patients tending to be younger. The colorectal cancer mouse model increases our understanding of human colorectal cancer characteristics and cancer prevention and treatment. Murine models of colorectal cancer can be divided into spontaneous, induced, transplanted tumor, and transgenic models. However, none recapitulate all the characteristics of human colorectal cancer. The use of a specific mouse colorectal cancer model to address specific colorectal cancer research issues is critical. This paper has examined research literature both domestic and foreign to provide a review of the research progress of different mouse models of colorectal carcinoma over the past 20 years. The aim is to establish a suitable mouse model for the study of colorectal cancer.
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PANG Lin-lin, ZHANG Hui-yong, YANG Guan-lin
2014,22(1):94-98, DOI: 10.3969/j.issn.1005-4847.2014.01.020
Abstract:
As one of the major domestic minipig strains, Guangxi Bama minipigs have the following characteristics: genetic stability, fecund species, lighter weight, large area of body surface covered with white hairs, many tissues and organs and biochemical indicators similar to those of humans and so on. All these characteristics make them being widely applied in medical research. Because of the similar anatomy and physiology in cardiovascular system, Bama minipigs have been used in the research of cardiovascular system. In our country, Bama minipigs are used for establishing models of cardiovascular diseases such as myocardial ischemia, patent foramen ovale and so on. Pigs are omnivore-animals and similar to human beings in lipid metabolism, so they can be used in the study of endocrine diseases. Bama minipigs have been used in modeling, genetic susceptibility and complication prevention of diabetes. Bama mini-pigs' digestive system is similar to that of humans, so they can be used as a model of digestive system diseases including chronic pancreatitis, rupture of colon and bilioenteric anastomosis. The aspect that large area of their body surface is covered with white hairs except their head and tail makes them ideal model of skin wound and healing of burns. Bama minipigs can be used for stomatological research for their similarity to human beings in the structure of the teeth and large crack. Bama minipigs have been applied for the research of pulp necrosis and the way of maxillary expansion. They are similar to human beings in anatomy, physiology and pathology, which makes them an appropriate provider for zenotransplantation. In the research of traditional Chinese medicine, Bama minipigs has been used as liver, spleen and femoral arteriovenous fistula hemorrhagic model to study curative effect and mechanism of traditional Chinese preparation.
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MA Chang, GUO Jianmin, XIE Songqiang, YANG Wei
2019,27(2):266-270, DOI: 10. 3969 / j.issn.1005-4847. 2019. 02. 022
Abstract:
Leukemia is often referred to as a “blood cancer”. The basic characteristic of the disease is thatleukemic cells become malignant and cause unrestricted proliferation in the bone marrow and other hematopoietic tissues.Then, these cells infiltrate all tissues and organs of the body causing various symptoms, and make patients prone to seriousinfections and life-threatening complications such as sepsis, hemorrhage, intestinal failure or hyperuricemia. Therefore,research on the treatment of leukemia using laboratory animal models is of great significance. For the study of leukemia,mice are similar to humans in terms of biology, genetics, and hematopoietic systems, and are, therefore, ideal models forleukemia research. This article reviews the mouse models of leukemia used commonly in studies both in China and abroad in the past 5 years.
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DING Jun-ying, GAO Xiang, HONG Yan-ying, GUI Hong, WEI Zhi-you, LU You-ran, AN Shi-dong, CUI Xu-ran, GUO Yu-hong, LIU Qing-quan
2017,25(6):600-604, DOI: 10.3969/j.issn.1005-4847.2017.06.003
Abstract:
Objective To explore the preparation of a rat model of pneumonia model induced by Pseudomonas aeruginosa(PA) using different methods,and to lay the foundation for further studies.Methods 48 SD rats were randomly divided into 4 groups:the control group (A),the intratracheal injection group (B),the trachea cannulation group (C) and the intranasal inoculation group (D).After intervention with different treatment modalities,the body weight,temperature,white blood cell count and lung pathological changes in the rats of all groups were detected at 5,10,15 days.Results 1.The behavior,body weight,temperature,leukocytes and pathological inflammatory changes of the lung in rats of the model groups were significantly different from that of control group.2.Pseudomonas aeruginosa was detected in rats of all the model groups,but the control group was negative.Conclusions Rat model of Pseudomonas aeruginosa infected pneumonia can be successfully established by intranasal inoculation.This method can avoid the inflammatory interference from operation,and is simple and suitable for popularization.
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MA Yuanyuan, LIU Chenghai, TAO Yanyan
2018,26(3):398-403, DOI: 10.3969/j. issn. 1005 -4847. 2018. 03. 020
Abstract:
Renal fibrosis is a common pathological pathway of chronic kidney diseases that leads to end?stage renal failure. The pathological changes include glomerulosclerosis and renal interstitial fibrosis. Ideal animal models for the study of pathologic mechanisms and drug development of chronic kidney disease are of great significance. At present, the method of establishment of animal models include drug or toxin induction, surgical models and gene knockout, etc. Different animal models have various characteristics of renal function and pathology, but can not completely simulate human chronic kidney disease, suggesting the complexity of chronic kidney diseases. So the preparation and research of the animal models is important for understanding the pathological mechanisms, prevention and treatment of renal fibrosis.
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LI Yuan, ZHAO Guang-ming, DONG Jian-xun, LU Guang-lin, ZHANG Xu-hui, WANG Le-ping
2014,22(1):63-66, DOI: 10.3969/j.issn.1005-4847.2014.01.012
Abstract:
Objective To observe the effects of different modeling methods on the wound morphology and healing time of chronic skin ulcers in diabetic rats. Methods SD rats (n=50) were randomly divided into five groups, 10 rats in each group: skin defect group (group QS: dermal deficiency), diabetes group (group DM: STZ injection+skin excision), diabetes plus Staphylococcus aureus group (group DMJJ: STZ injection+skin excision+bacterial infection), diabetes plus hydrocortisone group (group DMJS: STZ injection+skin excision+hydrocortisone intervention) and diabetes plus hydrocortisone and implantation of foreign body group (DMYW group: STZ injection+skin excision+hydrocortisone intervention + foreign body embedded). The rats were measured for body weight and wound healing every day, and blood glucose after stable diabetes once a week. The rats were sacrificed 12 days later and the skin lesions were examined by histopathology.Results The healing rate of the DMYW group was significantly slower than that in the other groups (P<0.01). At 12 days after modeling, the healing rate of the DMYW group was significantly lower than that of the remaining groups (P<0.01), while the healing rates were not significantly different among the remaining groups.Conclusions The modeling method of DMYW group can show skin wounds similar to the clinical characteristics of "Yin syndrome", and the addition of foreign body implantation significantly prolongs the rat skin healing time.
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LIU Yu-ting, GAO Yan-xiang, WANG Shan-shan, REN Wei, SUN Wei-liang, YU Chang-an, ZHENG Jin-gang
2017,25(4):399-403, DOI: 10.3969/j.issn.1005-4847.2017.04.010
Abstract:
Objective To establish a mouse model of aorta dissection (AD) by β-aminopropionitrile (BAPN) in drinking water + subcutaneously pumped angiotensin Ⅱ (Ang Ⅱ) infusion. Methods Forty 3-week-old C57B1/6J male mice were randomly divided into two groups. All animals received 0.1 g/kg/d BAPN in drinking water for 4 weeks. Then the BAPN drinking + saline infusion group and BAPN drinking + Ang Ⅱ infusion group received continuous saline or Ang Ⅱ (1,000 ng/kg/min) infusion, respectively, via subcutaneous osmotic minipump for 72 hour. The mice were restricted in a noninvasive computerized tail-cuff system and their arterial systolic blood pressure and heart rate were monitored. Autopsy was performed if a mouse died during the experiment. At the end of the experiment, mice were sacrificed by injection with an overdose of sodium pentobarbital and the aortas were harvested. The formation of aortic false lumen was observed by pathology using hematoxylin-eosin staining. Results The overall incidence of AD in the BAPN drinking administration +Ang Ⅱ infusion group was 95%, whereas the incidence of AD in the BAPN drinking administration +saline infusion group was only 5%. The mortality from dissecting aneurysm rupture was 24% in the BAPN drinking administration +Ang Ⅱ infusion group during the experiment. Pathological examination of the aortic cross-sections clearly showed the formation of blood-filled false lumens induced by Ang Ⅱ. Conclusions A mouse model with high incidence of aortic dissection is successfully established.
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LI Shumin, ZHANG Min, WANG Peng, HONG Fan, WANG Chen, ZHANG Yue, GENG Zhenyang, YANG Xinyu, HE Xiaoxiao, SUN Ying, YANG Fang
2018,26(5):548-553, DOI: 10.3969/j. issn. 1005 - 4847. 2018. 05. 002
Abstract:
Objective To provide a reference for studies of monitoring lung function in mice, this study was aimed to test the indexes of a non?invasive measurement of lung function in mice. Methods Lung function indexes of 460 C57BL/6 mice were detected by whole?body plethysmography. The results were analyzed, and the range of reference values was determined by the percentile method. Results Normal ranges for the following measures were found: inspiration time was 64. 7 (55. 30 -82. 60) ms, expiration time was 83. 4 (71. 70 -109. 20) ms, Rpef was 0. 21 (0. 16 -0. 28) ms, end?inspiratory pause was 2. 19 (1. 96 -3. 76) ms, end?expiratory pause was 1. 67 (0. 12 -9. 15) ms, tidal volume was 0. 44 (0. 25 -0. 58) mL, enhanced pause was 1. 29 (0. 91 -2. 00) ms, pause was 1. 18 (1. 00 -1. 64) ms, expiratory flow?50 was 0. 64 (0. 30 -0. 98) mL/ s, relaxation time was 39. 0 (32. 40 -51. 50) ms, peak inspiratory flow was 9. 74 (5. 33 -12. 83) mL/ s, peak expiratory flow was 9. 86 (5. 12 -13. 47) mL/ s, inspiratory frequency was 412 (331 - 474) BPM, and minute volume was 174. 4 (86. 69 -235. 04) mL. Conclusions The normal reference ranges from non?invasive lung monitoring in C57BL/6 mice can be used as a reference for basic research on respiratory diseases.
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SANG Ming, DAI Ming, ZHOU Li, LIU Jin-biao, GUO Ming, MA Tong-cui, XIAO Qian-hao, HO Wen-zhe
2015,23(1):18-24, DOI: 10.3969/j.issn.1005-4847.2015.01.004
Abstract:
Objectives To establish a simple, inexpensive and efficient technique for in vitro culture of monocyte-derived macrophages (MDM) from rhesus macaques of Chinese origin. Methods Peripheral blood of healthy rhesus macaques (Macaca mulatta) were obtained in heparinized vacutainer collection tubes. Peripheral blood mononuclear cells (PBMCs) were isolated from blood by Ficoll gradient centrifugation. Serum was isolated from peripheral blood of the autologous animals. PBMCs were plated in 48-well-plate (3×106 cells/well) or 96-well-plate (0.8×106 cells/well) for 24 h. After removal of non-adherent cells from the culture, monocytes were cultured in RPMI 1640 supplemented with different proportions (2%, 4%, 8%, 10%) of autologous serum or fetal calf serum (FCS) for 7 days. To examine the biological function of MDM, lipopolysaccharide (LPS) was added to MDM culture to determine inflammatory cytokine production. Also, MDM cultures were tested for the susceptibility to simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) infections. Results The cell cultures with RPMI1640 containing 2% autologous serum yielded the best results with regard to macrophage morphology, the response to LPS stimulation and susceptibility to SIV or SHIV infection. The purity of adherent macrophages under condition of 2% autologous serum culture was higher than 96%. Conclusions RPMI 1640 with 2% autologous serum is suitable for culture in vitro of peripheral blood monocytes from rhesus macaques. This technique is simple, inexpensive, no need for growth factor and highly effective to obtain adherent and well differentiated macaque monocytes. Therefore, this method provides an important tool for culture of macaque AIDS viruses and for related immunological research.
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LI Dongdong, WANG Li, ZHONG Jie, LING Chenqi, LIANG Yanping
2018,26(2):259-264, DOI: 10.3969/j. issn. 1005 -4847. 2018. 02. 021
Abstract:
Ovarian cancer is the fifth leading cause of cancer?related death in women. 75% of ovarian cancer patients were detected at an advanced stage. At present, the disease lacks effective early screening method and the clinical therapy effect is poor, which has become a serious threat to women’s health. The use of animal models of ovarian cancer is an important mean to elucidate the pathogenesis of the disease, and to screen effective diagnosis and treatment. The disease models are mainly divided into four types: spontaneous, induced, transplanted and gene intervention type. Mice, rats, hens, Mirotus Fortis and Mongolian gerbil are mainly selected to prepare animal models of ovarian cancer. Based on recent literature reports, we reviewed the preparation method of animal models of ovarian cancer and introduced the evaluation standards and main characteristics of these animal models.
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TENG Long, HONG Fang, HE Jian-cheng
2015,23(1):25-29, DOI: 10.3969/j.issn.1005-4847.2015.01.005
Abstract:
Objective To explore the oxidative stress in Parkinson's disease dyskinesia with Yin deficiency stirring wind pattern, and the interventional effect of compound formula rehmannia on the disease condition. Methods One hundred and twenty healthy male SD rats (body weight 180-200 g) were randomly divided into four groups: the control group, sham-operated group, model group, and Rehm group. The rat model with Parkinson's disease (PD) was established by injection of 6-hydroxyl dopamine to destroy the substantia nigra using the brain stereotaxic apparatus. Dyskinesia was induced in the PD rats by injection of levodopa into the brain. The dyskinesia PD model rats received intraperitoneal injection of levodopamine 50 mg/kg and benserazide 12.5 mg/kg for 2 weeks to induce Yin deficiency stirring wind pattern. The rats of Rehm group were given gastric gavage of compound formula rehmannia 2 mL/kg once a day for 4 weeks or 6 weeks. At the end of experiment (4 weeks and 6 weeks), neurobehavioral examination was performed, and the contents of SOD, MDA, GSH, and GSH-Px in the striatum tissue were assessed by colorimetry. Results In the LID group, the contents of SOD, GSH, GSH-Px in the striatum tissue were significantly lower than those in the normal control group and sham-operated group, and the malondialdehyde (MDA) content showed an increasing trend. In the compound rehmannia prescription group, the concentrations of SOD, GSH, GSH-Px in the striatum tissue showed an increasing trend, even more obvious along with the time course, and the malondialdehyde (MDA) content showed an decreasing trend, also even more obvious along with the time course. Conclusions The compound rehmannia prescription can improve the oxidative stress in rat models of Parkinson's disease dyskinesia with Yin deficiency stirring wind pattern. The interventional effect of compound rehmannia prescription may be mediated by scavenging free radicals and reducing the damage to the cells, thus, to alleviate the symptoms of Parkinson's disease dyskinesia.
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YANG Ting, LIN Zhijian, JIANG Zhuoxi, CHU Mengzhen, ZHANG Bing, ZOU Lina
2020,28(1):123-128, DOI: 10. 3969 / j.issn.1005-4847. 2020. 01. 018
Abstract:
Establishing a stable and reliable acute kidney injury model is an important means of researching acute kidney disease. Acute kidney injury models have various modeling method, different application scopes and diverse modeling standards. Acute kidney injury models were classified by reviewing the recent related literature and materials to analyze modeling method, pathological mechanisms, applications, modeling characteristics and other aspects. This work was conducted to provide promising references and considerable guidance for research and practice in treating acute kidney injuries.
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ZHU Hua, XU Li-li, BAO Lin-lin, DENG Wei, CHEN Ting, LU Qi, LI Feng-di, YUAN Jing, XU Yan-feng, HUANG-Lan, LI Yan-hong, LIU Jiang-ning, YAO Yan-feng, YU- Pin, YONG Wei-dong, WEI Qiang, ZHANG Lian-feng, QIN Chuan
2014,22(1):18-21, DOI: 10.3969/j.issn.1005-4847.2014.01.004
Abstract:
Objective The aim of this study was to establish a mouse model of H7N9 avian influenza A virus infection. Methods Seventy SPF healthy female BALB/c mice were used in this study. A/Anhui/1/2013 (H7N9) avian influenza virus was administered by intranasal instillation to BALB/c mice, inoculated in a dose of 50 μL 1×108, 1×107 or 1×106 TCID50, respectively, 10 mice in each group. Other 30 mice were used for virus titration and pathological examination. Ten mice were given saline as control group. The changes of body weight, clinical signs and death of the mice were observed every 24 h from 1 to 14 d. Blood and several organ samples were taken for pathological examination, and avian influenza A (H7N9) virus was detected with virus titration and immunohistochemistery (IHC). Results The mice developed typical clinical signs including body weight loss, ruffled fur and humped back. The peak of virus shedding from respiratory tract was observed on 2 days post inoculation (d.p.i.), and histopathological examination observed interstitial pneumonia. The virus was also detected in the brain, liver, spleen, kidney and intestine from inoculated mice. The inoculation of H7N9 virus elicited seroconversion titers up to 160. There was reduction of lymphocytes and increase of neutrophils in the blood. Conclusions The mouse model of H7N9 avian influenza virus infection established in this study show similar signs of human avian influenza. Therefore, it provides a useful working basis for research of the pathogenesis, drug development, and vaccine evaluation of this disease.
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XU Yu-rui, LI Jin-hua, SUN Bing-hua, XIA Dong-po, ZHU Yong, WANG Xi
2014,22(1):87-90, DOI: 10.3969/j.issn.1005-4847.2014.01.018
Abstract:
Objective To determine the blood biochemical parameters of wild and cage reared rhesus macaques in Anhui Province, and compare the differences between the two kinds of macaques and B virus (BV) positive and negative infection. Methods Fourteen blood biochemical indexes of Anhui rhesus macaques were measured with an automatic blood biochemical analyzer. The differences of biochemical parameters between wild and breeding, and BV positive and negative infection were analyzed. Results The blood biochemical indexes of males were higher than those of females. ALP, TG and GGT showed significant difference between males and females of wild macaques. ALP, ALB, Ca, TG, Cr and GGT showed significant difference between males and females of breeding macaques. The biochemical indexes of BV positive infected monkeys were higher than that of BV negative infected monkeys. Conclusion The blood biochemical parameters are different between wild and breeding macaques, males and females, and BV positive and negative infected monkeys.
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LIANG Juan, LIU Yue, YIN Xinhua
2019,27(1):110-114, DOI: 10. 3969 / j.issn.1005-4847. 2019. 01. 018
Abstract:
Cardiovascular disease (CVD) is a leading cause of human death worldwide, but its pathogenesis and prevention still need further research. Isoproterenol (ISO) is a β-adrenergic receptor agonist that acts directly or indirectly on the myocardium through inflammatory responses, oxidative stress, endoplasmic reticulum stress, autophagy, and apoptosis, which can cause mild myocardial injury, myocardial infarction, cardiac hypertrophy, and even heart failure. This review mainly focuses on the research on animal models of myocardial injury caused by ISO and attempts to describe its morphological and functional characteristics, as well as its pathogenesis.
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SUN Haiwei, SHI Xinjin, CHEN Yanyan, ZHONG Qiuping, ZHANG Meng, LYU Lu, WANG Jun, CHEN Hongjun
2019,27(5):571-576, DOI: 10. 3969 / j.issn.1005-4847. 2019. 05. 004
Abstract:
Objective The aim of this study was to establish an influenza A virus-induced inflammation model inmice to analyze the pathogenicity of influenza A virus. Methods Forty-four 5-week old SPF healthy female BALB/ c micewere used in this study. A/ swine/ Jiangsu/ C1/08 (H9N2) (H9C1), A/ swine/ Shandong/731/2009 (SD731) and A/Puerto Rico/8/34 ( H1N1) ( PR8) influenza viruses were administered by intranasal instillation to BALB/ c mice,inoculated in a dose of 50 μL 1 × 106 TCID50, respectively, 11 mice in each group. The changes of body weight, clinicalsigns and death of the mice were observed every 24 hours from 1 to 14 dpi (days post inoculation). Blood and lung sampleswere taken for virus titer and inflammation detection. Results Compared with the PBS control group, SD731 and PR8virus infected mice showed a strong inflammation, and the mortality rate of SD731 virus infected BALB/ c mice was 80%and that of the PR8 virus infection was 100%. H9C1 virus infection caused a mild inflammatory response compared toSD731 and PR8 virus infection, and no significant weight loss and no death from 1 to 14 dpi. Conclusions In this study,the successfully established mouse model of influenza A virus-infected inflammation provides a strategy for the study of thepathogenesis of influenza virus, and a useful working basis for research of the pathogenesis, drug development, and vaccine evaluation of this disease.
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SUN Bao-guo, XIANG Ting, LI Yu-long, CHEN Ze-xiong
2014,22(2):20-25, DOI: 10.3969/j.issn.1005-4847.2014.02.005
Abstract:
Objective To explore the establishing methods and differences of rat models of spleen deficiency and spleen deficiency liver cancer using the traditional Chinese medicine Dachengqi and Xiaochengqi decoctions.Methods Spleen-deficiency rat models were developed by multifactor methods: bitter-cold purgation (Dachengqi or Xiaochengqi decoction), cold-wet environment, tiredness, and fasting on alternate days for 30 days. Seven days after spleen-deficiency modeled,liver cancer in the spleen-deficiency rats and normal rats was developed by subcutaneously inoculation of Walker-256 carcinoma cell line in nude mice and then transplanted into rat livers. Liver cancer models were observed for 35 days. Sixty 3-week old male Wistar rats were randomly distributed into 4 groups: normal group, liver cancer model group, and Dachengqi and Xiaochengqi decoction groups. Degree of spleen deficiency, changes of the body-weight, survival time and tumor formation were recorded. Results Spleen deficiency rat models were successfully established. The weight gain of rats in the spleen-deficiency groups was significantly inhibited (P<0.01), and during the first 20 days (but not later) the average body weight of the Dachengqi decoction group was significantly higher than that of the Xiaochengqi decoction group (P<0.05). Spleen-deficiency scores of rats in the Xiaochengqi and Dachengqi groups were higher than those in the blank tumor group, especially in the Xiaochengqi group (P<0.01). The total tumor formation rate was 91.1% and 80% in the blank tumor groups, and 93.3% in both Xiaochengqi and Dachengqi groups, respectively. The average survival time of Xiaochengqi group was lower than that of the blank tumor and Dachengqi groups (P<0.01 and P<0.05). The cumulative survival rate of the Xiaochengqi group and rats with a higher spleen-deficiency score was lower than that of the other groups (P<0.05). Conclusions Xiaochengqi decoction may induce spleen deficiency more seriously than Dachengqi decoction, and spleen deficiency may be an important unfavorable prognostic factor for rat models of liver cancer.
