三氟淫羊藿素通过Notch1抑制大鼠慢性脑缺血损伤后过度自噬  

Trifluoro-icaritin inhibits excessive autophagy in rats after chronic cerebral ischemia damage through Notch1

作　　者：周海倩 张丽梅 葛清莲 蔡宇逸 刘瑞珍[2] 黎晓[2] 黄志华[2] ZHOU Hai-qian;ZHANG Li-mei;GE Qing-lian;CAI Yu-yi;LIU Rui-zhen;LI Xiao;HUANG Zhi-hua(Gannan Medical University;School of Basic Medicine of Gannan Medical University,Ganzhou,Jiangxi 341000)

机构地区：[1]赣南医学院 [2]赣南医学院基础医学院,江西赣州341000

出　　处：《赣南医学院学报》2020年第7期649-654,共6页JOURNAL OF GANNAN MEDICAL UNIVERSITY

基　　金：国家自然科学基金项目(319601902019);江西省自然科学基金项目(20192BAB205117);江西省研究生创新专项资金项目(YC2018-S416);江西省教育厅科技项目(GJJ70870)。

摘　　要：目的:研究三氟淫羊藿素(trifluoro-icaritin,ICTF)是否抑制大鼠慢性脑缺血诱导的过度自噬,并初步探讨其分子机制。方法:采用2-VO大鼠慢性脑缺血动物模型,连续给予ICTF治疗8周,Morris水迷宫实验探测大鼠认知功能;取大鼠海马区脑组织,运用qPCR方法检测自噬相关蛋白的mRNA表达水平,运用Western blot方法测定自噬相关蛋白LC3-Ⅱ和Notch1的表达水平。结果:三氟淫羊藿素明显改善慢性脑缺血诱导的大鼠认知功能障碍。与模型组相比,三氟淫羊藿素治疗组Atg13、LC3-Ⅱ和Beclin-1 mRNA的表达下降;与对照组相比,模型组LC3-Ⅱ蛋白的表达水平明显升高,Notch1表达降低,经三氟淫羊藿素治疗后,LC3-Ⅱ和Beclin-1蛋白表达量显著下降,Notch1表达升高。结论:三氟淫羊藿素可能通过抑制过度自噬和激活Notch1信号,促进慢性脑缺血后的神经功能修复。Objective:To explore the protective effect of trifluoro-icaritin(ICTF)on chronic cerebral ischemia damage rat and investigate the expression change of autophagy-related protein.Methods:To establish a stable,reliable,and bilateral common carotid arteries ligation(2-VO)model in rats.After 8 weeks treatment with ICTF,detect the cognitive function of rats by Morris water maze test;Extraction of brain tissue from rat hippocampus,using qPCR assay detect the mRNA expression of autophagy-related protein;The protein expression of LC3-Ⅱand Notch in half injury brain tissue were evaluated by western blot assay.Results:ICTF treatment improved cognitive impairment induced by chronic cerebral ischemia.Compared with the model group,the mRNA expression of Atg13,LC3-Ⅱand Beclin-1 were decreased in the ICTF treatment group.Compared with the control group,the expression of LC3-Ⅱprotein in the model group was in creased,Notch 1 protein was decreased.After treatment with ICTF,autophagy-related protein LC3-Ⅱdecreased but the expression of Notch 1 protein increased significantly.Conclusion:ICTF has therapeutic effects on chronic cerebral ischemia rats,it may inhibiting excessive autophagy and activating Notch 1 signal to promoting neuron regeneration after chronic cerebral ischemia.

关 键 词：自噬 慢性脑缺血 三氟淫羊藿素 NOTCH1 LC3-Ⅱ 

分 类 号：R285[医药卫生—中药学]