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-1 & beta;, 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.