Isoflurane ameliorates oxygen-glucose deprivation-induced cardiomyocyte injury through SIRT6/DNMT1 pathway

Abstract

The incidence of cardiovascular diseases is on the rise in the world, which poses a significant threat to human health. Myocardial ischemia can cause heart disease. Therefore, it is necessary to avoid myocardial hypoxia/reoxygenation (H/R) injury to attenuate the risk of heart disease. The present study focuses on the protective effect of isoflurane on H/R-induced cell injury through the Sirtuin 6 (SIRT6)/DNA (cytosine-5)-methyltransferase 1 (DNMT1) pathway. Quantitative reverse transcription PCR (RT‑qPCR) and Western blot analysis were used to measure protein levels and mRNA expression in H9c2 cells. Cell Counting Kit‑8 assays (CCK8 assay) was used to determine cell viability. The expression levels of pro-inflammatory molecule were assessed using commercial Enzyme-linked immunosorbent assay (ELISA) Kits. The ratio of cellular apoptosis was determined by flow cytometry. The contents of Lactate dehydrogenase (LDH), Cardiac Troponin I (cTnI), and Creatine Kinase MB (CK-MB) were detected using colorimetric assays. This study shows that Isoflurane reduces the expression of DNMT1 by activating SIRT6 in oxygen-glucose deprivation (OGD)-induced H/R injury. The damage of cardiomyocyte was decreased after Isoflurane treatment under OGD exposure condition. In addition, Isoflurane ameliorates OGD-induced inflammatory responses and cellular apoptosis in H9c2 cell via interaction with the SIRT6/DNMT1 pathway. Taken together, this study suggested the protective effect of Isoflurane on the process of OGD-induced damage and provided a new mechanism of action for Isoflurane in the treatment of H/R-induced cardiomyocyte injury.