阿尔茨海默病-痰瘀互结病证结合动物模型的建立与评价
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1.湖北中医药大学附属黄冈中医医院,湖北 黄冈 438000;2.湖北中医药大学老年医学研究所,武汉 430065; 3.北京中医药大学博士后流动站,北京 100029

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R-33

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Establishment of Alzheimer’s disease with intermingled phlegm and blood stasis in a transgenic mice model
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1.Huanggang Hospital of TCM, Hubei University of Traditional Chinese Medicine, Huanggang 438000, China. 2. Institute of Geriatrics, Hubei University of Chinese Medicine, Wuhan 430065. 3. Postdoctoral Station, Beijing University of Chinese Medicine, Beijing 100029

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    摘要:

    目的 本研究以探索建立一种可靠的阿尔茨海默病(Alzheimer’s disease,AD)与痰瘀互结证的病证结合动物模型为目的,为中医药防治 AD 提供相应的动物模型以及为建立病证结合动物模型的研究提供借鉴。 方法 以 APP / PS1 双转基因小鼠为 AD 模型动物,并以冰水浴模拟“瘀”的病理状态;给予高脂饮食饲喂模拟“痰”的病理状态;二者结合以模拟“痰瘀互结”的病理状态。不同组小鼠给予不同的处理,分别建立 AD-疾病模型组、AD- 痰证组、AD-瘀证组、AD-痰瘀互结组。同系非转基因 C57BL/ 6J 小鼠为对照组。 造模 14 d 后检测不同组小鼠的 AD 样行为学改变、舌象的客观变化、血液流变学和血脂改变,以及海马组织中相关蛋白含量的差异。 结果 造模 14 d 后,与对照组比较,AD 各组小鼠行为学均存在明显改变、相关蛋白含量均升高。 与 AD-模型组比较,AD-各病理状态组小鼠舌色偏暗红、AD-瘀证组血液流变指标及 AD-痰证组血脂指标均升高,其中 AD-痰瘀互结组相关指标均显著升高。 结论 通过冰水浴联合高脂饮食饲喂处理 APP / PS1 双转基因小鼠 14 d,可以成功建立 AD-痰瘀互结证的病证结合动物模型,此方法建模成型率高、与临床症状相贴合,可为后续相关研究提供稳定的动物实验载体。

    Abstract:

    Objective This study aimed to establish a reliable animal model of Alzheimer’ s disease (AD) with phlegm and stagnation to provide a corresponding animal model for the prevention and treatment of AD by Chinese medicine and to provide a reference on animal modelling method ology for the establishment of animal models combining disease and TCM evidence. Methods APP / PS1 2×Tg mice were used as AD model animals. The pathological state of “ stasis” was simulated by ice water bath and the pathological state of “ phlegm” was simulated by high-fat diet feeding. The two were combined to simulate the pathological state of “ phlegm and stasis interconnection”. The mice in different groups were treated differently: the AD-phlegm group was given a high-fat diet, the AD-stasis group was given an ice-water bath, the AD-phlegm-stasis group was given both a high-fat diet and an ice-water bath, and the AD-disease model group was left untreated. Non-transgenic C57BL/ 6J mice with the same genetic background were the control group. The differences in AD- like behavioral changes,objective changes in tongue image, blood rheology and lipid alterations and relevant protein content in hippocampal tissue were examined at 14 days after modeling. Results After 14 days of modeling, the AD-like behavioral changes and relevant protein content of mice in the AD groups were significantly changed compared with those in the control group. The tongue color was dark red in the AD-disease model group compared with result in the AD-model group; the hemorheology index of the AD-stasis group and the blood lipid index of the AD-phlegm group were increased. The related indexes of AD-phlegm-stasis interconnection group were significantly increased. Conclusions The combination of ice-water bath and high-fat diet to treat APP / PS1 mice for 14 days successfully established the combined animal model of AD-phlegm-stasis syndrome. This method has a high modeling rate, fits well with clinical symptoms and may represent a useful experimental animal system for subsequent studies.

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谭爱华,冉思邈,石和元,杨 硕.阿尔茨海默病-痰瘀互结病证结合动物模型的建立与评价[J].中国比较医学杂志,2022,32(4):39~46.

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  • 收稿日期:2021-08-11
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  • 在线发布日期: 2022-06-20
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