针刺研究

2020, v.45(06) 431-437

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电针对APP/PS1双转基因小鼠脑内海马区炎性反应及水通道蛋白4极性分布的影响
Effect of electroacupuncture on recognition memory and levels of Aβ, inflammatory factor proteins and aquaporin 4 in hippocampus of APP/PS1 double transgenic mice

王临梅;赵恬田;周寒璞;周孜奕;黄硕;凌银露;邵水金;
WANG Lin-mei;ZHAO Tian-tian;ZHOU Han-pu;ZHOU Zi-yi;HUANG Shuo;LING Yin-lu;SHAO Shui-jin;School of Basic Medicine, Shanghai University of Traditional Chinese Medicine;

摘要(Abstract):

目的:观察电针"百会""肾俞"穴对APP/PS1双转基因小鼠海马区胶质细胞活化、炎性反应因子表达及水通道蛋白4(AQP4)极性分布的影响,探讨电针对阿尔茨海默病(AD)的防治机制。方法:选取20只5月龄C57BL/6雄性APP/PS1转基因小鼠(模型组)及20只野生型C57BL/6小鼠(空白组),再各随机分为对照组和电针组,每组10只。电针组选取"百会""肾俞"穴进行电针干预,每次30 min,每日1次, 6 d为一疗程,共4个疗程。使用新物体识别实验的偏好指数(接触新物体的时间占总测试时间的百分比)评估各组小鼠的短期记忆能力;使用酶联免疫吸附法测定小鼠海马区β淀粉样蛋白(Aβ)_(1-40)和Aβ_(1-42)的含量;使用Western blot法测定海马区胶质纤维酸性蛋白(GFAP)、离子钙结合受体分子-1(Iba-1)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)表达量;使用免疫组织化学法测定海马区星形胶质细胞和小胶质细胞活化情况以及AQP4极性表达水平的改变。结果:对APP/PS1小鼠,电针组与对照组比较,对新物体偏好指数增加(P<0.05),海马区Aβ_(1-40)、Aβ_(1-42)的含量下降(P<0.01,P<0.05),GFAP、Iba-1、IL-1β、IL-6、TNF-α表达量降低(P<0.05),胶质细胞活化水平下降(P<0.05),AQP4极性分布水平增强(P<0.05)。结论:电针"百会""肾俞"穴可通过降低APP/PS1双转基因小鼠脑内海马区炎性反应水平,减少胶质细胞过度活化,从而改善AQP4极性分布紊乱,改善其短时记忆能力损伤,从而延缓AD的发展。
Objective To investigate the effect of electroacupuncture(EA) at "Baihui "(GV20) and "Shenshu "(BL23) on activation of glial cells, expression of inflammatory factor proteins and aquaporin 4(AQP4)in the hippocampus of amyloid precursor protein/presenilin-1(APP/PS1) transgenic mice, so as to explore its mechanisms underlying improvement of Alzheimer's disease(AD). Methods Twenty C57/BL6 background male APP695/PS1-dE9(APP/PS1) double transgenic mice(model group) and 20 wild type(WT) C57/BL6 mice(blank group) were respectively randomized into control and EA groups. EA(2 Hz/15 Hz, 1-2 mA) was applied to GV20 and bilateral BL23 for 30 min, once daily, 6 days a week for 4 weeks. The recognition memory ability was detected by novel object recognition tests in a behavior test box. The percentage of time spent in close interaction with novel object(C) relative to the total time was used to generate preference index. The contents of hippocampal β amyloid protein(Aβ)_(1-40) and Aβ_(1-42) were assayed using ELISA, and the expression levels of glial fibrillary acidic protein(GFAP), ionic calcium binding receptor molecule-1(Iba-1), interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) proteins in the hippocampus measured by Western blot. The activities of hippocampal astrocytes(GFAP-labelled cells), microglia(Iba-1-labelled cells) and the polarity expression of AQP4(for removing Aβ) were measured by immunohistochemistry. Results The preference index was significantly decreased in the model group relatively to the blank control group(P<0.05) and considerably increased in the model+EA group relatively to the model group(P<0.05), suggesting an improvement of the recognition memory after EA. The contents of Aβ_(1-40) and Aβ_(1-42), immunoactivity of GFAP and Iba-1, expression levels of GFAP, Iba-1, IL-1β, IL-6 and TNF-α proteins were significantly higher in the model group than in the blank control group(P<0.01,P<0.05), while the AQP4 immunoactivity was notably lower in the model group than in the blank control group(P<0.05). Compared with the model group, the levels of Aβ_(1-40) and Aβ_(1-42), GFAP, Iba-1, IL-1β, IL-6 and TNF-α proteins, and the percentage of Aβ plaque area were significantly decreased in the model+EA group(P<0.01,P<0.05), and the immunoactivity of AQP4 was significantly increased in the mo-del+EA group(P<0.05). No significant changes were found in the above-mentioned indexes in the blank+EA group relevant to the blank control group(P>0.05).Conclusion EA at GV20 and BL23 can reduce inflammatory reaction and Aβ level, suppress activation of astrocytes and microglia, and up-regulate expression of AQP4 in the hippocampus tissue in APP/PS1 transgenic mice, which may contribute to its effect in improving recognition memory ability, suggesting a role of EA intervention in delaying the development of AD via promoting the drainage of Aβ by the glymphatic system in the brain.

关键词(KeyWords): 阿尔茨海默病;电针;炎性反应因子;水通道蛋白4;胶质细胞
Alzheimer's disease;Electroacupuncture;Inflammatory factors;Aquaporin 4;Glial cells

Abstract:

Keywords:

基金项目(Foundation): 上海中医药大学预算内项目(No.A1-GY010134);上海中医药大学大学生创新活动计划(No.2019SHUTCM031);; 中国博士后科学基金面上项目(No.2019M661601)

作者(Author): 王临梅;赵恬田;周寒璞;周孜奕;黄硕;凌银露;邵水金;
WANG Lin-mei;ZHAO Tian-tian;ZHOU Han-pu;ZHOU Zi-yi;HUANG Shuo;LING Yin-lu;SHAO Shui-jin;School of Basic Medicine, Shanghai University of Traditional Chinese Medicine;

Email:

DOI: 10.13702/j.1000-0607.190923

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