Upregulation of miR-335 exerts protective effects against sepsis-induced myocardial injury

Septicemia is associated with excessive inflammation, oxidative stress and apoptosis, causing myocardial injury that results in high mortality and disability rates worldwide. The abnormal expression of multiple microRNAs (miRNAs/miRs) is associated with more severe sepsis-induced myocardial injury (SIMI) and miR-335 has been shown to protect cardiomyocytes from oxidative stress. The present study aimed to investigate the role of miR-335 in SIMI. An SIMI model was established by cecal ligation and puncture (CLP) in mice. An miRNA-335 precursor (pre-miR-335) was transfected to accelerate miR-335 expression and an miR-335 inhibitor (anti-miR-335) was used to inhibit miR-335 expression. CLP or sham surgery was performed on pre-miR-335, anti-miR-335 and wild-type mice and miR-335 expression was determined by reverse transcription-quantitative PCR. Inflammatory factors (TNF-α, IL-6 and IL-10) and troponin (cTNI), brain natriuretic peptide (BNP), creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were assessed using commercial kits. Apoptosis was detected by flow cytometry and cardiac function was assessed using a Langendorff isolated cardiac perfusion system. miR-335 expression was upregulated and an elevation in inflammatory factors and cTNI, BNP, CK, LDH and AST was observed. Compared with the wild-type control group, pre-miR-335 mice treated with CLP exhibited significantly reduced left ventricular development pressure, maximum pressure increased reduction rates, as well as decreased levels of TNF-α, IL-6 and IL-10, myocardial injury and apoptosis; by contrast, these features were amplified in CLP-treated anti-miR-335 mice. In conclusion, the upregulation of miR-335 exerted ameliorative effects on myocardial injury following sepsis and may indicate a novel therapeutic intervention for SIMI.