MiR-483-3p is involved in the pathogenesis of acute myocardial infarctions, but its association with myocardial ischemia reperfusion (IR) remains mostly unknown. In this study, an in vitro model of myocardial IR injury was established by putting H9c2 cells into hypoxia reoxygenation (HR) treatment to explore the effects and possible mechanisms of miR-483-3p in myocardial IR injury. HR exposure resulted in increased miR-483-3p levels in H9c2 cells. MiR-483-3p was overexpressed or downregulated in H9c2 cells by transfection of miR-483-3p mimic or miR-483-3p inhibitor. In HR-treated H9c2 cells, MiR-483-3p mimics inhibited cell viability, promoted lactate dehydrogenase release, and increased apoptosis, but miR-483-3p inhibitors caused the opposite effects. MDM4 was verified to be the target mRNA of miR-483-3p and negatively modulated by miR-483-3p. MiR-483-3p inhibitor upregulated MDM4 and Bcl-2, but downregulated p53 and Bax in HR-treated H9c2 cells, whereas miR-483-3p overexpression produced the opposite effects.. Moreover, MDM4 siRNA transfection partially reversed the role of miR-483-3p inhibition in HR injury and p53 pathway inactivation of H9c2 cells. In summary, by targeting the MDM4/p53 pathway, miR-483-3p inhibition may alleviate myocardial HR injury. MiR-483-3p may be a potential therapeutic target of myocardial IR injury.

MiR-483-3p参与了急性心肌梗死的发病机制，但其与心肌缺血再灌注（IR）的关联仍然未知。在这项研究中，在体外通过将H9c2细胞置于缺氧复氧（HR）处理中建立心肌IR损伤模型，以探讨miR-483-3p在心肌IR损伤中的作用及其可能的机制。HR暴露导致H9c2细胞中miR-483-3p水平升高。通过转染miR-483-3p模仿物或miR-483-3p抑制剂，H9c2细胞中的MiR-483-3p过表达或下调。在HR处理的H9c2细胞中，MiR-483-3p模仿物抑制细胞活力，促进乳酸脱氢酶释放，并增加细胞凋亡，但miR-483-3p抑制剂引起相反的作用。MDM4被证实是miR-483-3p的靶mRNA，并且被miR-483-3p负调控。在HR处理过的H9c2细胞中，MiR-483-3p抑制剂上调了MDM4和Bcl-2，但下调了p53和Bax，而miR-483-3p的过表达产生了相反的作用。MDM4 siRNA转染部分逆转了miR-483-3p抑制在HR损伤和H9c2细胞p53途径失活中的作用。总之，通过靶向MDM4 / p53途径，miR-483-3p抑制作用可以减轻心肌HR损伤。MiR-483-3p可能是心肌IR损伤的潜在治疗靶标。