MicroRNAs (miRs) were involved in numerous cardiovascular diseases, especially ischemic heart diseases, but the miR changes during cardiac ischemia-reperfusion (I/R) injury following sevoflurane (SEV) preconditioning are still unknown. This study aims to investigate the effect of miR-874 on cardiac I/R injury in mouse models pretreated with SEV. Following establishment of mouse models with myocardial I/R injury, mice were pretreated with SEV. The functional mechanism of miR-874 in I/R injury was explored when miR-874 and the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway were inhibited. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP biotin nick-end labeling (TUNEL) staining was used to detect cardiomyocyte apoptosis and dual luciferase reporter gene assay to identify the targeting relationship between miR-874 and STAT3. Expression of the JAK2/STAT3 signaling pathway and apoptosis-related genes was determined. Initially, upregulated miR-874 was observed in I/R mice. Then, miR-874 inhibition improved cardiac function of I/R mice, inhibited cardiomyocyte apoptosis (also shown as decreased Bcl-2 associated X protein B [Bax] and increased B-cell lymphoma-2 [Bcl-2]), and activated the JAK2/STAT3 signaling pathway. STAT3, a target gene of miR-874, was upregulated following miR-874 inhibition. Finally, we also observed that the effect of miR-874 was lost when the JAK2/STAT3 signaling pathway was blocked. The findings indicate miR-874 as a contributory role in cardiac I/R injury, with miR-874 inhibition alleviating cardiac I/R injury in mice following SEV pretreatment by targeting STAT3 through the JAK2/STAT3 signaling pathway.
Keywords: JAK2/STAT3 signaling pathway; STAT3; cardiac ischemia-reperfusion injury; microRNA-874; sevoflurane.
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