低氧预适应对小鼠海马神经保护作用机制研究——基于TSC1/mTOR/自噬信号通路  

Mechanism of hypoxic preconditioning on neuroprotective effect of mouse hippocampus——Based on TSC1/mTOR/autophagy signaling pathway

作　　者：齐瑞芳[1,2] 李娜 吕军[1,2] 石瑞丽 马宝慧[1,2] 时静华 郝肖琼[1,2] 邵国 QI Ruifang;LI Na;LV Jun;SHI Ruili;MA Baohui;SHI Jinghua;HAO Xiaoqiong;SHAO Guo(Preclinical and Forensic Medicine,Baotou Medical College of Inner Mongolia University of Science and Technology,Baotou 014040,China;Key Laboratory of Hypoxic Translational Medicine of Inner Mongolia,Baotou 014040,China;Center for Translational Medicine,Third People's Hospital,Longgang District,Shenzhen,Guangdong Province,shenzhen 518172,China)

机构地区：[1]内蒙古科技大学包头医学院基础医学与法医学院,包头014040 [2]内蒙古低氧适应转化医学重点实验室,包头014040 [3]广东省深圳市龙岗区第三人民医院转化医学中心,深圳518172

出　　处：《科技导报》2022年第13期107-113,共7页Science & Technology Review

基　　金：国家自然科学基金项目(81660307,82060337);内蒙古自治区自然科学基金项目(2019MS03093);内蒙古自治区高等学校科学研究项目(NJZY20171);包头医学院科学研究基金项目(BYJJ-BSJJ-202003);包头医学院花蕾计划项目(HL2020001,HL2020006,HL2020014,HL2020027)。

摘　　要：为研究低氧预适应(HPC)对小鼠海马神经保护作用的机制,采用Western Blot方法检测对照组、低氧组、低氧预适应组3组实验小鼠的TSC1、mTOR和磷酸化mTOR及LC3蛋白的表达,验证TSC1/mTOR/自噬通路是否参与HPC对小鼠海马的神经保护作用。通过体外HT22细胞转染TSC1-peGFP,给予低氧刺激后,采用MTS法检测细胞活性,进一步确定TSC1在低氧条件下的神经保护作用。结果显示,HPC可增加小鼠低氧耐受时间;与对照组相比,HPC组TSC1蛋白表达升高,磷酸化mTOR蛋白表达下降;体外转染eGFP-TSC1质粒组与空载组相比,细胞活性增强。结果表明HPC可能通过上调TSC1表达,下调mTOR磷酸化水平激活自噬对小鼠海马发挥神经保护作用。The purpose of this study is to understand the neuroprotective mechanism of hypoxic preconditioning(HPC)on mouse hippocampus.ICR mice were divided into the control group,hypoxia group and HPC group.Western Blot was used to detect the protein expression of TSC1,mTOR,phosphorylated mTOR and LC3 to ascertain whether TSC1/mTOR/autophagy pathway was involved in the neuroprotective effect of HPC on mice hippocampus.In order to further study the role of TSC1 in hypoxia,TSC1 pEGFP was transfected into HT22 cells in vitro.After hypoxia stimulation,the viability of cells was detected by MTS assay to determine the neuroprotective effect of TSC1 under hypoxia.Results showed that HPC increased the hypoxia tolerance time of mice,the expression of TSC1 protein increased and the expression of P-mTOR protein decreased in HPC group compared with those in the control group,and that the cell viability of TSC1-peGFP plasmid group was increased compared with that in the vector group.The results suggested that HPC played the neuroprotective role in the hippocampus of mice by activating autophagy through up-regulating the expression of TSC1 while down-regulating mTOR phosphorylation level.

关 键 词：低氧预适应 TSC1 MTOR 自噬 神经保护 

分 类 号：R338[医药卫生—人体生理学]