Trehalose Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting NLRP3-Mediated Pyroptosis

Myocardial ischemia/reperfusion (I/R) injury is a pathological damage secondary to myocardial ischemia that can further aggravate tissue and organ injuries. Therefore, there is an urgent need to develop an effective approach for alleviating myocardial I/R injury. Trehalose (TRE) is a natural bioactive substance that has been shown to have extensive physiological effects in various animals and plants. However, TRE’s protective effects against myocardial I/R injury remain unclear. This study aimed to evaluate the protective effect of TRE pre-treatment in mice with acute myocardial I/R injury and to explore the role of pyroptosis in this process. Mice were pre-treated with trehalose (1 mg/g) or an equivalent amount of saline solution for 7 days. The left anterior descending coronary artery was ligated in mice from the I/R and I/R + TRE groups, followed by 2-h or 24-h reperfusion after 30 min. Transthoracic echocardiography was performed to assess cardiac function in mice. Serum and cardiac tissue samples were obtained to examine the relevant indicators. We established an oxygen–glucose deprivation and re-oxygenation model in neonatal mouse ventricular cardiomyocytes and validated the mechanism by which trehalose affects myocardial necrosis via overexpression or silencing of NLRP3. TRE pre-treatment significantly improved cardiac dysfunction and reduced the infarct size in mice after I/R, accompanied by a decrease in the I/R-induced levels of CK-MB, cTnT, LDH, reactive oxygen species, pro-IL-1β, pro-IL-18, and TUNEL-positive cells. Furthermore, TRE intervention suppressed the expression of pyroptosis-related proteins following I/R. TRE attenuates myocardial I/R injury in mice by inhibiting NLRP3-mediated caspase-1-dependent pyroptosis in cardiomyocytes.