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电针通过激活PI3K/Akt信号通路改善大鼠脑缺血/再灌注损伤模型的学习和记忆功能。

Electroacupuncture improves learning and memory functions in a rat cerebral ischemia/reperfusion injury model through PI3K/Akt signaling pathway activation.

作者信息

Wang Hui-Ling, Liu Fei-Lai, Li Rui-Qing, Wan Ming-Yue, Li Jie-Ying, Shi Jing, Wu Ming-Li, Chen Jun-Hua, Sun Wei-Juan, Feng Hong-Xia, Zhao Wei, Huang Jin, Liu Ren-Chao, Hao Wen-Xue, Feng Xiao-Dong

机构信息

Rehabilitation Center, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan Province, China.

Department of Rehabilitation Medicine, Fujian University of Chinese Medicine, Fuzhou, Fujian Province, China.

出版信息

Neural Regen Res. 2021 Jun;16(6):1011-1016. doi: 10.4103/1673-5374.300454.

DOI:10.4103/1673-5374.300454
PMID:33269744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8224106/
Abstract

Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia, but the underlying mechanism has not yet been fully elucidated. Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment, and the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway plays an important role in autophagy regulation. To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models, we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method. Starting at 2 hours after modeling, electroacupuncture was delivered at the Shenting (GV24) and Baihui (GV20) acupoints, with a dilatational wave (1-20 Hz frequency, 2 mA intensity, 6 V peak voltage), for 30 minutes/day over 8 consecutive days. Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury, increased the mRNA expression levels of the PI3K/Akt signaling pathway-related factors Beclin-1, mammalian target of rapamycin (mTOR), and PI3K, increased the protein expression levels of phosphorylated Akt, Beclin-1, PI3K, and mTOR in the ischemic cerebral cortex, and simultaneously reduced p53 mRNA and protein expression levels. In the Morris water maze test, the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. In the spatial probe test, the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. Electroacupuncture stimulation applied to the Shenting (GV24) and Baihui (GV20) acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, China (approval No. 8150150901) on March 10, 2016.

摘要

电针已被广泛用于治疗脑缺血后的认知障碍,但其潜在机制尚未完全阐明。研究表明,自噬在认知障碍的形成和发展中起重要作用,磷酸肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路在自噬调节中起重要作用。为了探讨PI3K/Akt信号通路在电针治疗脑缺血/再灌注大鼠模型中的作用,我们首先采用线栓法阻断大脑中动脉建立大鼠脑缺血/再灌注模型。造模后2小时开始,于神庭(GV24)和百会(GV20)穴位进行电针治疗,采用疏密波(频率1 - 20Hz,强度2mA,峰值电压6V),每天治疗30分钟,连续治疗8天。我们的结果显示,电针可减小脑缺血/再灌注损伤大鼠模型的梗死体积,增加PI3K/Akt信号通路相关因子Beclin-1、雷帕霉素靶蛋白(mTOR)和PI3K的mRNA表达水平,增加缺血大脑皮层中磷酸化Akt、Beclin-1、PI3K和mTOR的蛋白表达水平,同时降低p53的mRNA和蛋白表达水平。在莫里斯水迷宫试验中,与未接受电针刺激的大鼠相比,接受电针刺激的大鼠找到隐藏平台的潜伏期显著缩短。在空间探索试验中,与未接受电针刺激的大鼠相比,接受电针刺激的大鼠穿越目标象限的次数增加。对神庭(GV24)和百会(GV20)穴位施加电针刺激可激活PI3K/Akt信号通路并改善大鼠学习记忆障碍。本研究于2016年3月10日获得中国河南中医药大学第一附属医院动物伦理委员会批准(批准号8150150901)。

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