草果知母汤介导mTOR信号通路对脑卒中大鼠神经元自噬与凋亡的影响  

Effects of Caoguo Zhimu decoction on autophagy and apoptosis in stroke rats through mTOR signaling pathway

作　　者：张高炼[1] 郭建辉 曾敬 李敏[1] 陈锐[1] 张晓宁[1] 刘姗姗[1] 梁韡斌 ZHANG Gao-Lian;GUO Jian-Hui;ZENG Jing(Department of Neurosurgery,the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine,Nanning 530023,Guangxi,China)

机构地区：[1]广西中医药大学第一附属医院仙葫院区颅脑外科,广西南宁530023

出　　处：《中国老年学杂志》2021年第13期2762-2768,共7页Chinese Journal of Gerontology

基　　金：国家自然科学基金(81660782)。

摘　　要：目的探究草果知母汤对脑卒中大鼠神经元自噬与凋亡的影响。方法SD大鼠适应1 w后进行脑缺血再灌注造模,根据神经功能评分进行随机分组,分为假手术组、脑缺血组、草果知母汤组、草果知母汤加雷帕霉素组,每组10只。给药7 d后进行神经功能评分和水迷宫测试,取脑用于2,3,5-三苯基氯化四氯唑(TTC)染色,免疫组化、电镜染色及免疫印迹检测。结果脑缺血再灌注造成大鼠神经功能与认知功能损伤,介导自噬过度激活,增加脑组织中的细胞凋亡,但草果知母汤给药则显著改善了大鼠神经功能与认知功能,减少了脑组织中神经元凋亡,抑制自噬激活。草果知母汤显著增加了哺乳动物雷帕霉素靶蛋白(mTOR)表达,而雷帕霉素则显著抑制了草果知母汤对脑缺血再灌注后损伤的治疗作用。结论草果知母汤通过增加mTOR表达,抑制神经元自噬,减少脑组织中细胞凋亡,改善脑缺血再灌注造成的神经功能与认知功能损伤。Objective To explore the effects of Caoguo Zhimu decoction on neuronal autophagy and apoptosis in stroke rats.Methods SD rats were adaptive for one week and ischemia/reperfusion were performed. And then the rats were randomly divided into sham group, ischemia/reperfusion group, Caoguo Zhimu decoction group and decoction combined with rapamycin group, 10 in each group. After drug administration seven days, neurological scores and water maze tests were performed. Brain tissues were taken for TTC staining, immunohistochemistry, Transmission electron microscopy staining, and Western blot.Results The ischemia/reperfusion successfully caused damage to the neurological and cognitive functions, resulting in excessive activation of autophagy and increased levels of apoptosis in brain. However, the administration of Caoguo Zhimu decoction significantly improved the neurological and cognitive function, as well as reduced apoptosis and inhibited autophagy activation in brain. In addition, Caoguo Zhimu decoction reversed increased expression of mTOR caused by cerebral ischemia/reperfusion, while rapamycin significantly abolished the effects of Cao Guo Zhimu decoction on injury after ischemia/reperfusion.Conclusions Caoguo Zhimu decoction could reduce the level of apoptosis in brain through increasing the expression of mTOR and inhibiting neuronal autophagy, which improves the neurological and cognitive impairment caused by ischemia/reperfusion.

关 键 词：草果知母汤 脑缺血再灌注 自噬 凋亡 哺乳动物雷帕霉素靶蛋白(mTOR) 

分 类 号：R743[医药卫生—神经病学与精神病学]