Inhibition of miR-218-5p reduces myocardial ischemia-reperfusion injury in a Sprague-Dawley rat model by reducing oxidative stress and inflammation through MEF2C/NF-κB pathway.

ABSTRACT

Following myocardial ischemia, myocardial reperfusion injury causes oxidative stress (OS) and inflammation, leading to myocardial cell apoptosis and necrosis. Recently, emerging studies have shown that microRNAs (miRNAs) contribute to the pathophysiology associated with myocardial ischemia-reperfusion (I/R). In this study, we conducted both in-vitro and in-vivo experiments to explore the role of miR-218-5p in ischemia-reperfusion (I/R)- or oxygen and glucose deprivation/reperfusion (OGD/R)-mediated cardiomyocyte injury. A total 44 Sprague-Dawley (SD) rats were used, and randomly divided into four groups, control group (n = 11), miR-218-5p-in group (n = 11), I/R group (n = 11), I/R + miR-218-5p-in group (n = 11). Our data showed that miR-218-5p was overexpressed in H9C2 cardiomyocytes under OGD/R treatment. miR-218-5p inhibition reduced the lactate dehydrogenase (LDH) activity and the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expression of tumor necrosis factor alpha (TNF-α), interleukin (IL-1ß), and IL-6. Oppositely, miR-218-5p overexpression aggravated OGD/R-mediated damage on H9C2 cells, whereas nuclear factor kappa B (NF-κB) pathway inhibition or myocyte enhancer factor 2C (MEF2C) upregulation reversed miR-218-5p mimics-mediated effects. Bioinformatics analysis predicted that miR-218-5p targeted and dampened its expression, which was testified by the dual-luciferase reporter assay and RNA pull-down assay. In vivo, inhibiting miR-218-5p declined LDH activities and ROS, MDA and SOD levels in rat myocardial tissues under I/R injury, alleviated myocardial fibrosis and inflammatory reactions, and reduced myocardial infarction area. Overall, inhibition of miR-218-5p choked oxidative stress and inflammation in myocardial I/R injury via targeting MEF2C/NF-κB axis, thus relieving the disease progression.