Effects of resveratrol on tolerance to ischemia/reperfusion injury in aged male mice: Role of autophagy and apoptosis

Abstract

AbstractAged myocardium is more susceptible to ischemia/reperfusion (I/R) injury. Autophagy and apoptosis play important roles in cardiac I/R injury. However, whether resveratrol can reduce the I/R vulnerability of aged myocardium by regulating apoptosis and autophagy remains unclear. The present study aimed to investigate the effect of resveratrol on the tolerance to I/R injury in aged male mice and to determine the contribution of apoptosis and autophagy. We used aged C57 mice as our research subjects. The hearts of mice were isolated after 6 weeks of intragastric administration with resveratrol and subsequently perfused with Krebs–Henseleit buffer to produce the I/R model. We found that resveratrol alleviated cardiac I/R injury in aged mice, but not in SIRT1+/− mice. Aged mice exhibited decreased LC3 and Beclin1 expressions, which were significantly rescued by resveratrol treatment. In addition, resveratrol decreased the expression of Bax and the activity of Caspase‐3, while increasing the expression of Bcl‐2 and the activity of SIRT1 in aged mouse hearts. Coimmunoprecipitation assays revealed that resveratrol facilitated the binding of Bax to Bcl‐2 and the dissociation of Bcl‐2 from Beclin1 in aged mouse myocardium. Conversely, SIRT1 knockout enhanced the formation of the Beclin1/Bcl‐2 complex and disrupted the interaction between Bcl‐2 and Bax. The above results indicate that resveratrol can reduce the vulnerability of myocardial I/R injury in senile myocardium by inhibiting apoptosis and upregulating autophagy through the SIRT1 signaling pathway.