NLRP3 Inflammasome Activation-Mediated Pyroptosis Aggravates Myocardial IschemiaReperfusion Injury in Diabetic Rats

Abstract EN

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.