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

作者：Qiu, Zhen; Lei, Shaoqing; Zhao, Bo; Wu, Yang; Su, Wating; Liu, Min; Meng, Qingtao; Zhou, Bin; Leng, Yan; Xia, Zhong-yuan^*

来源：Oxidative Medicine and Cellular Longevity, 2017, 2017: 9743280.

DOI：10.1155/2017/9743280

• ISCHEMIA-REPERFUSION INJURY
• BUTYL HALOPERIDOL IODIDE
• CELL-DEATH
• BAY 11-7082
• OXIDATIVE STRESS
• PORE FORMATION
• KAPPA-B
• MECHANISM
• CARDIOPROTECTION
• APOPTOSIS

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, 30mM) 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.

• 出版日期2017
• 单位武汉大学