Myocardial infarction represents one of the severe cardiovascular diseases and is one of the high-risk factors for mortality, and ischemia/reperfusion (I/R) injury is one of the risk factors that contribute to the high mortality of myocardial infarction. MicroRNAs have been proven as key regulators in various diseases including myocardial infarction. The present study was sought to determine the role of miR-703 in the myocardial I/R injury and to explore detailed mechanisms. Hypoxia/reoxygenation (H/R) treatment repressed cell viability, increased cytotoxicity and pyroptosis in mouse cardiomyocytes. More importantly, we found that miR-703 was suppressed in mouse cardiomyocytes upon H/R stimulation. Restoration of miR-703 expression in mouse cardiomyocytes counteracted the H/R-induced cytotoxicity and pyroptosis in mouse cardiomyocytes; and the effects of miR-703 inhibition on cell viability and pyroptosis were similar to that of H/R treatment in mouse cardiomyocytes. In a further investigation, we found that NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) was targeted and repressed by miR-703 in mouse cardiomyocytes. NLRP3 knockdown also attenuated H/R-induced cytotoxicity and pyroptosis in mouse cardiomyocytes. In the mechanistic perspective, NLRP3 enforced expression disrupted the protective effects of miR-703 restoration on the H/R-induced cytotoxicity and pyroptosis in mouse cardiomyocytes. Our results for the first time demonstrate the protective actions of miR-703 in the H/R-induced mouse cardiomyocyte injury. More importantly, miR-703 protects against H/R-induced cardiomyocyte injury via inhibiting the NLRP3/caspase-1-mediated pyroptosis.

心肌梗塞是严重的心血管疾病之一，并且是导致死亡的高风险因素之一，而缺血/再灌注（I / R）损伤是导致心肌梗塞高死亡率的危险因素之一。MicroRNA已被证明是包括心肌梗塞在内的各种疾病的关键调控因子。寻求本研究以确定miR-703在心肌I / R损伤中的作用并探索详细的机制。缺氧/复氧（H / R）处理可抑制小鼠心肌细胞的细胞活力，增加的细胞毒性和凋亡。更重要的是，我们发现在H / R刺激下，小鼠心肌细胞中的miR-703被抑制。小鼠心肌细胞中miR-703表达的恢复抵消了H / R诱导的小鼠心肌细胞毒性和细胞凋亡。miR-703抑制作用对小鼠心肌细胞活力和凋亡的影响与H / R处理相似。在进一步的研究中，我们发现miR-703在小鼠心肌细胞中靶向并抑制了含NOD，LRR和吡喃结构域的蛋白3（NLRP3）。NLRP3敲低还减弱了H / R诱导的小鼠心肌细胞的细胞毒性和焦磷酸化。从机理的角度来看，NLRP3强制表达破坏了miR-703还原对小鼠心肌细胞H / R诱导的细胞毒性和细胞凋亡的保护作用。我们的结果首次证明了miR-703在H / R诱导的小鼠心肌细胞损伤中的保护作用。更重要的是，miR-703通过抑制NLRP3 / caspase-1介导的细胞凋亡来预防H / R诱导的心肌细胞损伤。