Abstract

To investigate the effects of microRNA-29a (miR-29a) on myocardial ischemia-reperfusion (I/R) injury and its specific mechanisms, we used H9C2 myocardial cells to establish a myocardial ischemia model by hypoxia/reoxygenation (H/R), and microRNA-29a inhibitor was interfered. Annexin V/propidium iodide and flow cytometry were used to detect the effects of cell death. C57 mice were used to establish were used to establish the I/R injury model, and H&E staining was used to detect pathologic damage to heart tissues. The expressions of miR-29a silent information regulator factor 2–related enzyme 1 (SIRT1) and nucleotide-binding oligomerization domain like receptor protein 3 (NLRP3), as well as pyroptosis-related proteins were determined by quantitative reverse-transcription polymerase chain reaction and Western blot analysis. The serum levels of 2-hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase-1 (LDH), creatine kinase (CK), creatine kinase MB activity (CK-MB), IMA, and inflammatory factors in I/R rats were significantly up-regulated. In the I/R group, the expression of miR-29a was significantly up-regulated while SIRT1 was remarkably down-regulated. Dual luciferase reporter assay showed SIRT1 was a direct target of miR-29a. Inhibition of miR-29a significantly up-regulated the expression of peroxisome proliferator-activated receptor gamma coactivator-1α/nuclear respiratory factor-2 and endothelial nitric oxide synthase while remarkably down-regulating levels of inducible nitric oxide synthase and malondialdehyde in I/R. The oxidative stress that was induced by I/R injury was also suppressed by inhibition of miR-29a. All these effects of miR-29a inhibition were reversed by small interfering SIRT1. The in vitro H/R results showed that NLRP3–caspase-1–mediated pyroptosis was activated in H/R but was significantly inhibited by the inhibition of miR-29a. Inhibition of miR-29a improved myocardial I/R injury by targeting SIRT1 through suppressing oxidative stress and NLRP3-mediated pyroptosis.