Yang Qing-Hua, Guo Ling, Chen Qing, Wu Kai-Hui, Wu Yan-Jun, Jia Yan, Zhu Shu-Juan, Tang Cheng-Lin, Sheng Hua-Jun
Department of Teaching and Research of Anatomy, Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, China.
1Department of Teaching and Research of Anatomy, Institute of Neuroscience, 2 College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.
Zhen Ci Yan Jiu. 2018 Apr 25;43(4):215-20. doi: 10.13702/j.1000-0607.170460.
To observe the effect of electroacupuncture (EA) intervention on learning-memory ability and the expression of senile plaques (SP), amyloid precursor protein (APP), β-secretase 1(BACE 1) and insulin degrading enzyme (IDE) in the hippocampus in APP/presenilin 1 (PS 1) double transgenic Alzheimer's disease (AD) mice, so as to reveal its mechanisms underlying improvement of AD.
A total of 18 male APP/PS 1 double transgenic AD mice were randomly divided into model, EA-2-week and EA-3-week groups (=6 in each). The control group was consisted of 6 male wild mice. EA (2 Hz, 2 mA) was applied to "Baihui" (GV 20) and bilateral "Shenshu" (BL 23) for 15 min, once a day, with 7 days being a therapeutic course, 2 or 3 courses altogether and with an one day's interval between every two courses. The spatial learning-memory ability was assessed using Morris water maze test during 5 days' training. The immunoactivity of SP in the hippocampus tissue was detected by immunohistochemistry, and the expression levels of APP, BACE 1 and IDE in the hippocampus were analyzed by Western blot.
Following modeling, the escape latency and path length of hidden platform tests were significantly increased (<0.01, <0.05), and the platform crossing time of spatial probing test significantly decreased (<0.01) in the model group compared with the control group. After EA intervention, the escape latency on the 5 day of training, and the path length on the 4 and 5 day of training in both EA-2-week and EA-3-week groups were significantly shorter relevant to the model group (<0.01), and those of the EA-3-week group were considerably shorter than those of the EA-2-week group in the escape latency and path length (<0.05, <0.01). The platform crossing times of spatial probing test were significanthy increased in both EA-2-week and EA-3-week groups in comparison with the model group (<0.01), and that of the EA-3-week group was considerably increased compared with the EA-2-week group (<0.05). Immunohistochemical staining showed that the number of SP in the hippocampus was markedly increased in the model group compared with the control group (<0.01), and was markedly reduced in both EA-2-week and EA-3-week groups (<0.01), and that of the EA-3-week group was significantly decreased compared with the EA-2-week group (<0.01). The expression levels of hippocampal APP and BACE 1 proteins were significantly higher in the model group than in the control group (<0.01), and that of hippocampal IDE was markedly lower in the model group than in the control group (<0.01). After EA, the increased expression levels of APP and BACE 1 proteins and the decreased expression level of IDE in the EA-2-week and EA-3-week groups were significantly inhibited (<0.01). The effects of EA-3-week were significantly stronger than those of EA-2-week in down-regulating the expression of APP and BACE 1 proteins and up-regulating the expression of IDE (<0.01, <0.05).
EA stimulation of GV 20 and BL 23 can improve the learning-memory ability in APP/PS 1 double transgenic AD mice, which may be related to its effects in down-regulating the expression of SP, APP and BACE 1 proteins and up-regulating the expression of IDE protein in the hippocampus.
观察电针（EA）干预对APP/早老素1（PS1）双转基因阿尔茨海默病（AD）小鼠学习记忆能力及海马区老年斑（SP）、淀粉样前体蛋白（APP）、β-分泌酶1（BACE 1）和胰岛素降解酶（IDE）表达的影响，以揭示其改善AD的作用机制。
将18只雄性APP/PS1双转基因AD小鼠随机分为模型组、电针2周组和电针3周组，每组6只。对照组为6只雄性野生型小鼠。采用2 Hz、2 mA的电针刺激“百会”（GV 20）和双侧“肾俞”（BL 23），每次15分钟，每日1次，7天为1个疗程，共治疗2或3个疗程，疗程间间隔1天。在5天的训练期间，采用Morris水迷宫试验评估空间学习记忆能力。采用免疫组织化学法检测海马组织中SP的免疫活性，采用蛋白质印迹法分析海马中APP、BACE 1和IDE的表达水平。
造模后，与对照组相比，模型组隐藏平台试验的逃避潜伏期和路径长度显著增加（<0.01，<0.05），空间探索试验的平台穿越时间显著减少（<0.01）。电针干预后，电针2周组和电针3周组训练第5天的逃避潜伏期、训练第4和5天的路径长度均较模型组显著缩短（<0.01），且电针3周组的逃避潜伏期和路径长度均显著短于电针2周组（<0.05，<0.01）。电针2周组和电针3周组空间探索试验的平台穿越时间均较模型组显著增加（<0.01），且电电针3周组的平台穿越时间显著多于电针2周组（<0.05）。免疫组织化学染色显示，与对照组相比，模型组海马中SP数量显著增加（<0.01），电针2周组和电针3周组均显著减少（<0.01），且电针3周组显著少于电针2周组（<0.01）。模型组海马APP和BACE 1蛋白表达水平显著高于对照组（<0.01），海马IDE表达水平显著低于对照组（<0.01）。电针后，电针2周组和电针3周组APP和BACE 1蛋白表达水平的升高及IDE表达水平的降低均受到显著抑制（<0.01）。电针3周组下调APP和BACE 1蛋白表达及上调IDE表达的作用显著强于电针2周组（<0.01，<0.05）。
电针刺激GV 20和BL 23可改善APP/PS1双转基因AD小鼠的学习记忆能力，其机制可能与下调海马中SP、APP和BACE 1蛋白表达及上调IDE蛋白表达有关。
