Activation of autophagy inhibits nucleotide‐binding oligomerization domain‐like receptor protein 3 inflammasome activation and attenuates myocardial ischemia‐reperfusion injury in diabetic rats

• DOI: 10.1111/jdi.13235
• Publication Date: 2020-02-17T01:54:41Z
• Authors: Dengwen Zhang; Yi He; Xiaodong Ye; Yin Cai; Jindong Xu; Liangqing Zhang; Mingyi Li; Hao Liu; Sheng Wang; Zhengyuan Xia
• Keywords: Diabetic Cardiomyopathy; Hypoxia; Creatine kinase

Abstract Aims/Introduction Diabetic hearts are more vulnerable to ischemia‐reperfusion injury (I/RI). The activation of nucleotide‐binding oligomerization domain‐like receptor protein 3 (NLRP3) inflammasome can mediate the inflammatory process, and hence might contribute myocardial I/RI. Activation autophagy eliminate excess reactive oxygen species alleviate I/RI in diabetes. present study aimed investigate whether diabetic through inhibition NLRP3 activation. Materials Methods A dose 65 mg/kg streptozotocin was given by tail vein injection establish a type 1 diabetes model rats. left anterior descending coronary artery ligated for 30 min followed reperfusion 2 h model. H9C2 cardiomyocytes were exposed high glucose (33 mmol/L) subjected hypoxia–reoxygenation (6 hypoxia 4 reoxygenation). Results rats showed significant cardiac (decreased LC3‐II/I increased p62) that concomitant with (increased NLRP3, apoptosis‐related spots cleaved caspase‐1, interleukin‐18, interleukin‐1β) severe (elevated creatine kinase band, lactate dehydrogenase larger infarct size). However, administration rapamycin, an inhibitor autophagy, activate resulted inflammasome, finally alleviated In vitro , inhibited while activating aggravating injury, but rapamycin reversed these adverse effects glucose. Conclusion suppress formation which turn attenuates