Myocardial ischaemia-reperfusion (I/R) injury is a serious illness with high morbidity and mortality. Mounting evidence indicates the utility of sevoflurane (SEV) in the treatment of myocardial I/R injury. This study aimed to explore the molecular mechanisms underlying the protective action of SEV against myocardial I/R injury. A rat model of myocardial I/R injury was established, and I/R rats were treated with different concentrations of SEV. MicroRNA-203 (miR-203) and doublecortin (DCX) expression levels were determined using reverse transcription-quantitative polymerase chain reaction. Putative target relationship between miR-203 and DCX was explored using dual-luciferase reporter gene assay and RNA-binding protein immunoprecipitation assay. Ischaemia-reperfusion rats were treated with SEV, miR-203 antagomir or sh-DCX, followed by determination of oxidative stress- and inflammation-related factor levels using nitrite and enzyme-linked immunosorbent assays, and that of apoptosis-related factors using Western blot analysis. The apoptotic rate of myocardial tissues was determined using TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, and the infract area was evaluated using triphenyltetrazolium chloride staining. The results showed miR-203 was poorly expressed and DCX was highly expressed in myocardial tissues of I/R rats. Sevoflurane was found to elevate miR-203, and miR-203, in turn, could target and reduce DCX expression. Sevoflurane, miR-203 overexpression or DCX silencing resulted in declined oxidative stress, inflammation, apoptosis and infarct area, ultimately alleviating myocardial I/R injury. Collectively, these findings showed that SEV-activated miR-203 exhibited suppressive effects on myocardial I/R injury in rats and highlighted the SEV/miR-203/DCX axis as a promising therapeutic target for myocardial I/R injury management.
Keywords: doublecortin; inflammation; microRNA-203; myocardial ischaemia-reperfusion injury; oxidative stress; sevoflurane.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.