Melatonin receptor‐mediated protection against myocardial ischemia/reperfusion injury: role of SIRT1

Abstract Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion ( MI / R ) injury by reducing oxidative stress. Activation of silent information regulator 1 ( SIRT 1) signaling also reduces MI / R injury. We hypothesize that melatonin may protect against MI / R injury by activating SIRT 1 signaling. This study investigated the protective effect of melatonin treatment on MI / R heart and elucidated its potential mechanisms. Rats were exposed to melatonin treatment in the presence or the absence of the melatonin receptor antagonist luzindole or SIRT 1 inhibitor EX 527 and then subjected to MI / R operation. Melatonin conferred a cardioprotective effect by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase release, upregulating SIRT 1, B cl‐2 expression and downregulating B ax, caspase‐3 and cleaved caspase‐3 expression. Melatonin treatment also resulted in reduced myocardium superoxide generation, gp91 phox expression, malondialdehyde level, and increased myocardium superoxide dismutase ( SOD ) level, which indicate that the MI / R ‐induced oxidative stress was significantly attenuated. However, these protective effects were blocked by EX 527 or luzindole, indicating that SIRT 1 signaling and melatonin receptor may be specifically involved in these effects. In summary, our results demonstrate that melatonin treatment attenuates MI / R injury by reducing oxidative stress damage via activation of SIRT 1 signaling in a receptor‐dependent manner.