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

Abstract

Aged 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.