中国医科大学学报2024,Vol.53Issue(7):603-609,7.DOI:10.12007/j.issn.0258-4646.2024.07.005
脑缺血/再灌注后大鼠心肌自噬的变化及分子调节机制
Changes in myocardial autophagy and its regulatory mechanisms after cerebral ischemia/reperfusion in rats
摘要
Abstract
Objective To investigate the dynamic changes and molecular mechanisms of myocardial injury and autophagy as the body's self-protective mechanism at different time points after cerebral ischemia/reperfusion(CI/R).Methods A CI/R model was established in male Sprague-Dawley rats using the Longa thread method.Rats that underwent CI/R following middle cerebral artery occlusion were classified into 6-,12-,24,and 48-hour groups according to the reperfusion time.The concentrations of reactive oxygen species and reac-tive nitrogen species were measured to evaluate myocardial oxidative stress.Cardiomyocyte apoptosis and autophagosomes were observed in the myocardium.Additionally,dynamic changes in myocardial autophagy,autophagic flux,and protein and gene expression of auto-phagy regulators were detected.Results Oxidative-stress-induced injury and apoptosis were observed in the myocardium after CI/R.The number of autophagosomes in cardiomyocytes increased,peaking in the 12 h group,and autophagic flux was impaired during the first 12 h after CI/R.Beclin 1,mammalian target of rapamycin(mTOR),and adenosine monophosphate-activated protein kinase(AMPK)expression levels in the myocardium increased during the first 48 h after CI/R,peaking in the 12 h group.This was consistent with changes in autophagy,which showed significant differences compared with the control group.Conclusion These results indicated that autophagy plays a protective role against CI/R-induced myocardial injury.Furthermore,Beclin 1-mediated autophagy/apoptosis and mTOR-mediated autophagy mutual feedback pathways play important roles in the regulation of autophagy.关键词
缺血/再灌注损伤/自噬/Beclin 1/mTORKey words
ischemia-reperfusion injury/autophagy/Beclin 1/mTOR分类
医药卫生引用本文复制引用
李晓婷,聂宏光,樊建华..脑缺血/再灌注后大鼠心肌自噬的变化及分子调节机制[J].中国医科大学学报,2024,53(7):603-609,7.基金项目
辽宁省重点研发计划指导计划(2018225077) (2018225077)