中国医科大学学报2026，Vol.55Issue(2)：122-126,132,6.DOI:10.12007/j.issn.0258-4646.2026.02.005
早期跑步通过HSPA5/PINK1/Parkin信号通路介导的线粒体自噬改善脑缺血小鼠的记忆功能
Early running improves memory function in cerebral ischemic mice via mitochondrial autophagy mediated by the HSPA5/PINK1/Parkin signaling pathway
摘要
Abstract
Objective To explore how early running improves memory function in mice with cerebral ischemia/reperfusion(I/R)injury by modulating PINK1/Parkin-mediated mitophagy through heat shock protein A5(HSPA5).Methods Male BALB/c mice were randomly divided into the sham,running,I/R,running+I/R,running+I/R+3-MA(autophagy inhibitor),running+I/R+scrambled siRNA,and run-ning+I/R+HSPA5 siRNA groups,with eight mice in each group.After seven days of I/R,the neurological function of mice in each group was evaluated by the Longa score,cerebral infarct volume by TTC staining,memory function by water maze analysis,serum levels of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β)and interleukin-10(IL-10)by ELISA,mRNA level of HSPA5 in the ischemic penumbra of mice by real time quantitative PCR,and protein expressions of PINK1 and Parkin in the ischemic penumbra by Western blotting.Results Compared with the sham group,the I/R group had increased neurological deficit score and infarct volume,decreased time spent in the target quadrant and number of platform crossings,increased serum levels of TNF-α and IL-1β,and decreased level of IL-10(all P<0.05).Compared with the I/R group,the running+I/R group had decreased neurological deficit score and infarct volume,increased time spent in the target quadrant and the number of platform crossings,decreased serum levels of TNF-α and IL-1β,and increased level of IL-10(all P<0.05).Compared with the running+I/R group,the running+I/R+HSPA5 siRNA group had decreased time spent in the target quadrant and the number of platform crossings,increased serum levels of TNF-α and IL-1β,and decreased level of IL-10(all P<0.05).Compared with the sham group,the I/R group had increased expression of HSPA5 mRNA and PINK1 and Parkin protein in the ischemic penumbra(all P<0.05).The expression of HSPA5 mRNA and PINK1 and Parkin protein was further increased in the running+I/R group compared with the I/R group(all P<0.05),while the expression of PINK1 and Parkin protein was decreased in the running+I/R+3-MA and the running+I/R+HSPA5 siRNA groups compared with the running+I/R group(all P<0.05).Conclusion Our study provided evidence showing that early running could improve memory function in mice with I/R injury by activation of PINK1/Par-kin-mediated mitophagy through the upregulation of HSPA5.关键词
跑步/缺血/再灌注/热休克蛋白A5/PINK1/Parkin信号通路/自噬Key words
running/heat shock protein A5/ischemia/reperfusion/PINK1/Parkin signaling pathway/mitophagy分类
医药卫生引用本文复制引用
彭志锋,李加善,张继红..早期跑步通过HSPA5/PINK1/Parkin信号通路介导的线粒体自噬改善脑缺血小鼠的记忆功能[J].中国医科大学学报,2026,55(2):122-126,132,6.基金项目
山西省科技厅基础研究项目(202303021211326) （202303021211326）
