NLRP3 Inflammasome Activation‐Mediated Pyroptosis Aggravates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats

Abstract

The reactive oxygen species‐ (ROS‐) induced nod‐like receptor protein‐3 (NLRP3) inflammasome triggers sterile inflammatory responses and pyroptosis, which is a proinflammatory form of programmed cell death initiated by the activation of inflammatory caspases. NLRP3 inflammasome activation plays an important role in myocardial ischemia/reperfusion (MI/R) injury. Our present study investigated whether diabetes aggravated MI/R injury through NLRP3 inflammasome‐mediated pyroptosis. Type 1 diabetic rat model was established by intraperitoneal injection of streptozotocin (60 mg/kg). MI/R was induced by ligating the left anterior descending artery (LAD) for 30 minutes followed by 2 h reperfusion. H9C2 cardiomyocytes were exposed to high glucose (HG, 30 mM) conditions and hypoxia/reoxygenation (H/R) stimulation. The myocardial infarct size, CK‐MB, and LDH release in the diabetic rats subjected to MI/R were significantly higher than those in the nondiabetic rats, accompanied with increased NLRP3 inflammasome activation and increased pyroptosis. Inhibition of inflammasome activation with BAY11‐7082 significantly decreased the MI/R injury. In vitro studies showed similar effects, as BAY11‐7082 or the ROS scavenger N‐acetylcysteine, attenuated HG and H/R‐induced H9C2 cell injury. In conclusion, hyperglycaemia‐induced NLRP3 inflammasome activation may be a ROS‐dependent process in pyroptotic cell death, and NLRP3 inflammasome‐induced pyroptosis aggravates MI/R injury in diabetic rats.