Sevoflurane exerts protection against myocardial ischemia–reperfusion injury and pyroptosis through the circular RNA PAN3/microRNA-29b-3p/stromal cell-derived factor 4 axis

Abstract

ObjectiveSevoflurane is suggested to exert protective functions against myocardial ischemia–reperfusion injury (MIRI). However, the particular mechanism remains elusive. Therefore, this research explored the mechanism of sevoflurane in MIRI-induced damage and pyroptosis. MethodsSubsequent to gain-or loss-of-function assays or/and sevoflurane treatment, the MIRI model was developed in rats. Cardiac function and body and heart weight of rats were evaluated, followed by measurement of apoptosis and creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), and pyroptosis-related protein levels. After loss-of-function assays or/and sevoflurane treatment in human cardiomyocytes (HCMs), the hypoxia/reoxygenation (H/R) model was constructed. In HCMs, cell viability, apoptosis, and pyroptosis-related proteins were detected. Circular RNA PAN3 (circPAN3), microRNA (miR)-29b-3p, and stromal cell-derived factor 4 (SDF4) expression was determined in rat myocardial tissues and HCMs. Mechanistically, interactions among circPAN3, miR-29b-3p, and SDF4 were analyzed. ResultsMIRI modeling increased miR-29b-3p expression and diminished circPAN3 and SDF4 expression in H/R-treated HCMs and MIRI rats, which was nullified by sevoflurane preconditioning. Mechanistically, circPAN3 negatively targeted miR-29b-3p to upregulate SDF4. Moreover, sevoflurane preconditioning reduced heart weight/body weight ratio, LDH, CK-MB, myocardial infarct size, left ventricular end-diastolic pressure, apoptosis, and pyroptosis, while elevating the increase and decrease of left ventricular pressure (±dp/dt max) and left ventricular systolic pressure in MIRI rats. In addition, sevoflurane preconditioning augmented viability while diminishing apoptosis and pyroptosis in H/R-treated HCMs. Moreover, circPAN3 silencing or miR-29b-3p overexpression abrogated alleviatory effects of sevoflurane on myocardial injury and pyroptosis in vitro. ConclusionSevoflurane treatment ameliorated myocardial injury and pyroptosis in MIRI via circPAN3/miR-29b-3p/SDF4 axis.