基于数据挖掘的慢性疲劳综合征动物模型的评价
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1.河南中医药大学;2.河南中医药大学 药学院

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国家自然科学基金(82274119);河南省重大专项(221100310400);岐黄学者(国中医药人教函2022-6);中原学者工作站项目(224400510011);2022年河南省博士后科研资助项目(HN2022079)


Evaluation of an animal model of chronic fatigue syndrome based on data mining
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1.Henan University of Chinese Medicine;2.Henan University of Chinese Medicine,Zhengzhou

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    摘要:

    目的:研究慢性疲劳综合征动物模型的应用情况,为其动物实验方法和模型完善提供参考。方法:以“慢性疲劳综合征,动物模型”“Chronic fatigue syndrom,animal model”等为检索词,在中国知网、万方、PubMed数据库进行检索,整理2000年7月至2023年7月慢性疲劳综合征动物模型的文献,对实验动物、造模方法、阳性药、检测指标等内容进行整理,建立数据库进行统计、分析。结果:共纳入有效文献155篇;实验动物以SPF级、周龄为6-8周的雄性SD大鼠最多,体重集中在180-220g;小鼠应用最多的是18-22g、周龄为6-8周的雄性KM小鼠;应用最多的阳性药是人参皂苷片;应用最多的造模方法是“强制冷水游泳+慢性束缚”法,造模周期多集中在14天,大多采用边造模边干预的方式;检测指标以行为学为主,主要包括力竭游泳实验、旷场实验、鼠尾悬吊实验、Morris水迷宫实验以及动物一般状态观察,其次是血清生化指标,检测最多的是血清MDA、SOD、TNF-α、IL-1β、CORT、IL-2、IFN-γ、ACTH、GSH-Px、IgG、IgA、IL-6等;根据研究目的不同选择其余多种检测指标,包括脾脏、胸腺等脏器指数测定、HE病理染色和超微结构电镜检测的形态学指标、免疫组化相关指标、时荧光定量PCR检测法检测的CRH、Smad4、BDNF、CREB、IFN-γ、NRF-1、TFAM、Tlr4等的相关mRNA表达指标,Western blot法检测的BDNF、CREB、ERK、Bmal1、Clock、NGF、PGC-1α、SIRT1、Smad4、Caspsae-3等的相关蛋白表达指标。结论:目前慢性疲劳综合征的发病机制尚不明确,动物模型以“强制冷水游泳+慢性束缚”的应激造模方法为主,模拟人类身体和心理疲劳状态;动物模型成模标准尚无统一规定,模型评价方式以各种行为学实验单独或组合应用为主,多数文献中客观评价指标多用于病因病机猜想的论证及干预措施有效性评价;各项检测指标应用结果表明慢性疲劳综合征可能与炎症反应、神经功能障碍和线粒体功能异常等因素有关,其发病机制中可能存在免疫功能、能量代谢、细胞增殖和细胞死亡的异常状况,挖掘内容有望为模型应用提供参考,为模型完善提供思路。

    Abstract:

    Objective To study the application of the animal model of chronic fatigue syndrome, and to provide reference for its animal experimental methods and model improvement. Methods Using "chronic fatigue syndrome, animal model" and "chronic fatigue syndrom, animal model" as search terms, we searched in China Knowledge, Wanfang and PubMed databases. Literature on animal models of chronic fatigue syndrome was compiled from July 2000 to July 2023, and experimental animals, modeling methods, positive drugs, and detection indexes were sorted out, and a database was established for statistics and analysis. Results A total of 155 articles were included; the most experimental animals were male SD rats of SPF grade and 6-8 weeks of age, with weights of 180-220g; the most used mice were male KM mice of 18-22g and 6-8 weeks of age; the most used positive drug was ginseng saponin tablets; the most used modeling method was the method of "forced cold water swimming + chronic restraint"; the most used modeling method was the method of "forced cold water swimming + chronic restraint"; the most used modeling method was the method of "forced cold water swimming + chronic restraint". +The most widely used modeling method is the "forced cold water swimming" method, and the modeling cycle is mostly concentrated in 14 days, and most of them adopt the method of intervention while modeling; the testing indexes are mainly behavioral, which mainly include the exhaustion swimming experiment, the open field experiment, the rat-tail suspension experiment, the Morris water maze experiment, and the observation of the general state of the animals, and the second is the serum biochemical indexes, and the most frequently detected indexes are serum MDA, SOD, TNF-alpha, IOD, and IBP, TNF-α, IL-1β, CORT, IL-2, IFN-γ, ACTH, GSH-Px, IgG, IgA, IL-6, etc. The rest of the indicators were selected according to the research purpose, including the indexes of spleen, thymus, etc., the morphological indicators detected by HE staining and ultrastructural electron microscopy, the immunohistochemistry-related indicators, the CRH and Smilax detected by fluorescence PCR, the CRH, the Smilax, the Smilax, and the Smilax. The mRNA expression indexes of CRH, Smad4, BDNF, CREB, IFN-γ, NRF-1, TFAM, Tlr4, etc., and the protein expression indexes of BDNF, CREB, ERK, Bmal1, Clock, NGF, PGC-1α, SIRT1, Smad4, Caspsae-3, etc., were determined by Western blot method. and other related protein expression indicators. Conclusion At present, the pathogenesis of chronic fatigue syndrome is still unclear, and the animal model is mainly based on the stress modeling method of "forced cold water swimming + chronic restraint", which simulates the physical and mental fatigue state of human beings; there is no uniform regulation on the criteria for the formation of animal models, and the evaluation of the model is based on the application of a variety of behavioral experiments individually or in combination, and the objective evaluation indexes are mostly used to argue the etiology of the disease and evaluate the effectiveness of interventions. The objective evaluation indexes are mostly used to prove the conjecture of etiology and evaluate the effectiveness of interventions; the results of the application of various test indexes show that chronic fatigue syndrome may be related to inflammatory response, neurological dysfunction, and mitochondrial dysfunction, and there may be abnormalities in the pathogenesis of immune function, energy metabolism, cell proliferation, and cell death, which is expected to provide reference for the application of the model, and to provide ideas for the model"s refinement. The excavated content is expected to provide reference for the application of the model and provide ideas for the improvement of the model.

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  • 收稿日期:2023-10-04
  • 最后修改日期:2024-03-04
  • 录用日期:2024-03-21
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