MicroRNA‑132 promotes oxidative stress‑induced pyroptosis by targeting sirtuin 1 in myocardial ischaemia‑reperfusion injury

• Published in: International journal of molecular medicine Vol. 45; no. 6; pp. 1942 - 1950
• Main Authors: Zhou, Yan, Li, Kun-Sheng, Liu, Lu, Li, Shi-Liang
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.06.2020; Spandidos Publications UK Ltd
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Autophagy; Cancer; Caspase 1 - genetics; Coronary vessels; Dehydrogenases; Endothelium; Enzymes; House mouse; Hypoxia; Interleukins; Ischemia; Journalists; Kinases; Laboratory animals; Luciferase; Malondialdehyde - metabolism; Mice; Mice, Inbred C57BL; MicroRNA; MicroRNAs; MicroRNAs - genetics; Myocardial Reperfusion Injury - genetics; Myocardial Reperfusion Injury - metabolism; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; NF-E2-Related Factor 2 - genetics; Nitric oxide; Nitric Oxide Synthase Type III - genetics; Nitrogen oxides; Oxidative stress; Oxidative Stress - genetics; Polymerase chain reaction; Proteins; Pyroptosis - genetics; Reperfusion injury; Scientific equipment industry; Signal Transduction - genetics; Sirtuin 1 - genetics; Studies; Superoxide Dismutase - genetics; Superoxides; Tumor necrosis factor-TNF; United States; China
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2020.4557

The present study aimed to investigate the roles of miR‑132 in myocardial ischaemia/reperfusion (I/R) injury and the underlying mechanisms. The myocardial I/R model was established using C57BL/J6 mice. Haematoxylin and eosin staining was performed to observe the injury of myocardial tissues. Commercial kits were used to measure the levels of serum myocardial enzymes and inflammatory factors. The in vitro I/R model was established by the hypoxia/reoxygenation method using H9C2 cells. A dual luciferase reporter assay was used to confirm the binding of miR‑132 and sirtuin 1 (SIRT1). Cell pyroptosis was determined using flow cytometry. Reverse transcription‑quantitative PCR was performed to determine the expression of miR‑132, SIRT1 and inflammatory factors. The levels of peroxisome proliferator‑activated receptor gamma coactivator (PGC)‑1α/nuclear factor erythroid‑2‑related factor 2 (Nrf2) signalling, oxidative stress and pyroptosis‑related proteins were detected by western blotting. Apparent histologic injury and elevated levels of serum myocardial enzymes and inflammatory factors were observed in the myocardial I/R model. miR‑132 was significantly upregulated and SIRT1 was markedly downregulated in I/R myocardial tissues. miR‑132 directly targeted SIRT1 and negatively regulated the expression of SIRT1. PGC‑1α, Nrf2, endothelial nitric oxide synthase and superoxide dismutase levels were significantly decreased, while inducible nitric oxide synthase and malondialdehyde levels were significantly increased by I/R induction. The pyroptosis‑related proteins NLRP3, caspase‑1 and interleukin (IL)‑1β were also significantly elevated by I/R induction. Inhibition of miR‑132 activated PGC‑1α/Nrf2 signalling and inhibited oxidative stress and the expression of the pyroptosis‑related proteins NLRP3, caspase‑1 and IL‑1β, which were all reversed by inhibiting SIRT1 with EX527. The findings of the present study indicated that inhibition of miR‑132 may ameliorate myocardial I/R injury by inhibiting oxidative stress and pyroptosis through activation of PGC‑1α/Nrf2 signalling by targeting SIRT1.