Changes in myocardial autophagy and its regulatory mechanisms after cerebral ischemia/reperfusion in rats
10.12007/j.issn.0258-4646.2024.07.005
- VernacularTitle:脑缺血/再灌注后大鼠心肌自噬的变化及分子调节机制
- Author:
Xiaoting LI
1
;
Hongguang NIE
;
Jianhua FAN
Author Information
1. 中国医科大学 附属第四医院院内感染管理办公室,沈阳 110032
- Keywords:
ischemia-reperfusion injury;
autophagy;
Beclin 1;
mTOR
- From:
Journal of China Medical University
2024;53(7):603-609
- CountryChina
- Language:Chinese
-
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.
