MiR-208a participates with sevoflurane post-conditioning in protecting neonatal rat cardiomyocytes with simulated ischemia-reperfusion injury via PI3K/AKT signaling pathway.

Abstract

We aimed to evaluate the role of miR-208a in sevoflurane post-conditioning protecting neonatal rat cardiomyocytes with simulated ischemia reperfusion injury (SI/RI) via PI3K/AKT signaling pathway. The cardiomyocytes of healthy neonatal rats were extracted as the Normal group. Other cardiomyocytes were used to establish the SI/RI model. Sevoflurane post-conditioning, miR-208a inhibitor, or PI3K/AKT pathway activator were used in the treatment of cardiomyocytes. The cell viability, cell cycle, apoptosis, levels of superoxide dismutase (SOD), malondialdehyde (MDA), miR-208a and mRNA, expression of PI3K, AKT, and autophagy-related factors in each group were measured and compared. Monodansylcadaverine (MDC) was used to measure the fluorescence intensity of autophagosomes. In neonatal rat cardiomyocytes with SI/RI, the expression of miR-208a and MDA, apoptosis and the expression of autophagy-related factors increased, with PI3K/AKT pathway inhibited, SOD level decreased, cell viability reduced, and the fluorescence intensity of autophagosomes enhanced (all p<0.05). Sevoflurane post-conditioning can promote the increase of SOD and the decrease of MDA in cardiomyocytes with SI/RI, with PI3K/AKT pathway activated, viability of cardiomyocytes enhanced, apoptosis reduced, the expression of autophagy-related factors and the fluorescence intensity of autophagosomes inhibited (all p<0.05). Sevoflurane post-conditioning combined with miR-208a inhibitor or PI3K/AKT pathway activator further promoted the above-mentioned effects (all p<0.05). Our results indicate that the inhibited expression of miR-208a suppresses the expression of autophagy-related factors, enhances cell viability of cardiomyocytes, and reduces apoptosis, thereby protecting neonatal rat cardiomyocytes with SI/RI.