MiR-183-5p Enhances Autophagy by Targeting IRS1/PI3K-Oxidative Stress Signaling Pathway via Affecting Sepsis-Induced Cardiac Dysfunction

This study aimed to research the specific of miR-183-5p on sepsis-induced cardiac dysfunction. The cecal ligation and puncture method (CLP) establish an animal model of sepsis. All animals were randomly divided into five groups, namely, control group, CLP+miR-183-5p mimic NC group, CLP+miR-183-5p mimic group, CLP+miR-183-5p inhibitor NC group and CLP+miR-183-5p inhibitor group. According to the results, compared with control group, CLP+miR-183-5p mimic/inhibitor NC group exhibited focal degeneration and necrosis of myocardial cells, infiltration of inflammatory cells, a dramatically increased apoptosis level of myocardial cells and cardiac ultrasonic parameters decreased evidently. In addition, with the remarkably increased protein expression of IRS1, the protein expressions of p-PI3K and p-mTOR rose in myocardium, while those of LC3II and Beclin declined. Moreover, compared with CLP+miR-183-5p mimic NC group, the myocardial cells showed a pathological improvement tendency, the apoptosis level and the protein expressions of IRS1, p-PI3K and p-mTOR in myocardium dropped markedly, LVAW; d, LVAW; s, LVPW; d and EF, and LC3II and Beclin associated with autophagy evidently rose in CLP+miR-183-5p mimic group. Compared with CLP+miR-183-5p inhibitor NC group, the indicators of CLP+miR-183-5p inhibitor group tended to deterio-rate. LPS was utilized to induce myocardial cell injury in in vitro experiments. It was found that miR-183-5p mimic down-regulated the protein expressions of IRS1, p-PI3K, p-Akt and p-mTOR, and up-regulated the expressions of LC3II and Beclin, while miR-183-5p inhibitor had the opposite effect. In a word, miR-183-5p enhanced autophagy by targeting IRS1 to regulate the PI3K/Akt/mTOR signaling pathway, thereby influencing sepsis-induced cardiac dysfunction.