Downregulation of microRNA-155 stimulates sevoflurane-mediated cardioprotection against myocardial ischemia/reperfusion injury by binding to SIRT1 in mice.

Abstract

The inhaled sevoflurane has been demonstrated to protect against myocardial ischemia/reperfusion (I/R) injury. However, the relative mechanisms of sevoflurane-mediated cardioprotection remain largely unknown. This study intends to explore the effect of miR-155 on the sevoflurane-mediated cardioprotection by regulating Sirtuin 1 (SIRT1) in mouse models of myocardial I/R. Left anterior descending coronary artery ligation was used to induce models of myocardial I/R in mice. The I/R mice were treated with sevoflurane, sevoflurane + mimics negative control (NC) or sevoflurane + miR-155 mimics. The expression of microRNA-155 (miR-155) and SIRT1 was examined by quantitative real-time polymerase chain reaction and Western blot assay. Then cardiac functions and hemodynamic alterations were evaluated. Evans blue-2,3,5-triphenyltetrazolium chloride and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay staining methods were adopted to evaluate infarct size and cardiomyocyte apoptosis, respectively. In the I/R mice, miR-155 was expressed at a high level and SIRT1 at a low level. SIRT1 was confirmed to be a target gene of miR-155. The treatment of sevoflurane could reduce miR-155 expression and increased SIRT1 expression in the myocardial tissues, under which conditions, cardiac functions were promoted, accompanied by reduced infarct size and inhibited cardiomyocyte apoptosis. In response to miR-155 upregulation, the sevoflurane-treated I/R mice showed reduced cardiac functions, and increased infarct size and cardiomyocyte apoptosis. The findings obtained in this study provide evidence suggesting that miR-155 targets and negatively regulates SIRT1 expression, a mechanism by which the protection of sevoflurane is inhibited against myocardial I/R in mice.