针刺研究

2021, v.46(09) 763-768

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电针联合二甲双胍对APP/PS1小鼠认知功能和老年斑的影响
Comparative analysis of electroacupuncture, metformin and their combination on cognitive function and senile plaques of cerebral cortex and hippocampus in APP/PS1 mice

夏青倩;张皓;郭震;蔡子凌;沈自豪;朱淑娟;唐成林;黄思琴;盛华均;
XIA Qing-qian;ZHANG Hao;GUO Zhen;CAI Zi-ling;SHEN Zi-hao;ZHU Shu-juan;TANG Cheng-lin;HUANG Si-qin;SHENG Hua-jun;Department of Anatomy,Neuroscience Research Center,Chongqing Medical University;School of Traditional Chinese Medicine,Chongqing Medical University;

摘要(Abstract):

目的:比较分析电针、二甲双胍和二者联合对APP/PS1小鼠认知功能的影响,探索一种更优的治疗方式。方法:将3月龄雄性APP/PS1小鼠随机分为模型组、药物组、电针组和针药联合组,每组6只;另选取6只同月龄雄性野生C57小鼠作为对照组。电针组选取"百会""肾俞"穴行电针干预,15 min/次,1次/d,每周休息1 d;药物组予二甲双胍300 mg·kg~(-1)·d~(-1)灌胃治疗;针药联合组行药物和电针共同干预,均连续干预4周。采用Morris水迷宫实验检测小鼠认知功能,HE染色观察大脑皮层及海马神经元形态,免疫组织化学法观察大脑皮层及海马老年斑(SPs),Western blot法检测大脑皮层及海马中与SPs形成密切相关的β-分泌酶(BACE1)和胰岛素降解酶(IDE)的表达。结果:与对照组相比,模型组小鼠逃避潜伏期延长(P<0.01),穿越原平台次数减少(P<0.01),大脑皮层及海马神经元排列紊乱,形态不完整,SPs数量明显增加(P<0.01),BACE1蛋白表达明显升高(P<0.01),IDE蛋白表达明显降低(P<0.01)。与模型组相比,药物组、电针组和针药联合组小鼠逃避潜伏期缩短(P<0.01),穿越原平台次数增加(P<0.01),海马神经元形态、数量、排列改善,大脑皮层及海马区SPs数量减少(P<0.01),BACE1蛋白表达降低(P<0.01),IDE蛋白表达升高(P<0.01)。与药物组和电针组相比,针药联合组小鼠认知功能、大脑皮层及海马区SPs的数量、BACE1和IDE蛋白表达等的变化更显著(P<0.01)。结论:针药联合治疗改善AD小鼠的认知功能及SPs的效果更好,可能与调节BACE1和IDE生成过程有关。
Objective To compare the effect of electroacupuncture(EA), metformin and EA plus metformin on the cognitive ability and senile plaques(SPs) in cerebral cortex and hippocampus of Alzheimer's disease(AD) mice, so as to explore a better treatment method for AD. Methods Twenty-four male APP/PS1 mice were randomly divided into model, metformin(medication), EA and EA+medication groups, with 6 mice in each group. Other 6 male wild C57 mice were used as the control group. EA(2 Hz, 1.0 mA) was applied to "Baihui"(GV20) and "Shenshu"(BL23) for 15 min, once a day, for 4 weeks, with 1 day's off every week. The mice of the medication group received gavage of metformin(300 mg·kg~(-1)·d~(-1)) once a day for 4 weeks. Morris water maze tests were used to assess the cognitive function of mice. H.E. staining was used to observe the histopathological changes of neurons in the cortex and hippocampus. Immunohistochemical method was used to observe the cerebral cortex and hippocampal SPs. The expression levels of SPs formation-related proteins: β-site amyloid precursor protein cleaving enzyme 1(βACE1) and insulin-degrading enzyme(IDE) in the cortex and hippocampus were detected by Western blot.Results Compared with the control group, the escape latency, number of SPs and the expression of βACE1 in the cortex and hippocampus were ob-viously increased(P<0.01), and the times of platform quadrant crossing and the expression of IDE protein were markedly decreased in the model group(P<0.01). In comparison with the model group, the escape latency, and the number of SPs and expression of βACE1 proteins in the cortex and hippocampus in the 3 treatment groups were significantly down-regulated(P<0.01), while the times of platform quadrant crossing, and the expression of IDE protein in both cortex and hippocampus of the three treatment groups were considerably up-regulated(P<0.01). Comparison among the three treatment groups showed that the therapeutic effect of EA+medication was significantly superior to that of medication and simple EA in down-regulating the escape latency, the number of SPs and expression of βACE1 in the cortex and hippocampus(P<0.01), and in up-regulating the times of the platform quadrant crossing, and expression of IDE protein in both cortex and hippocampus(P<0.01). No significant differences were found between the simple medication and simple EA in all the indexes mentioned above(P>0.05).Conclusion EA, metformin and EA plus metformin can improve cognitive ability and relieve SP formation in cerebral cortex and hippocampus in AD mice, which may be associated with their functions in down-regulating the expression of βACE1 and up-regulating the expression of IDE. The therapeutic effects of EA plus metformin are apparently better than those of simple EA and simple metformin.

关键词(KeyWords): 阿尔茨海默病;电针;二甲双胍;老年斑;大脑皮层;海马;认知功能
Alzheimer's disease;Electroacupuncture;Metformin;Senile plaques;Cerebral cortex;Hippocampus;Cognitive ability

Abstract:

Keywords:

基金项目(Foundation): 重庆市教委青年项目(No.KJQN201900)

作者(Author): 夏青倩;张皓;郭震;蔡子凌;沈自豪;朱淑娟;唐成林;黄思琴;盛华均;
XIA Qing-qian;ZHANG Hao;GUO Zhen;CAI Zi-ling;SHEN Zi-hao;ZHU Shu-juan;TANG Cheng-lin;HUANG Si-qin;SHENG Hua-jun;Department of Anatomy,Neuroscience Research Center,Chongqing Medical University;School of Traditional Chinese Medicine,Chongqing Medical University;

Email:

DOI: 10.13702/j.1000-0607.20210454

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