Isoflurane pretreatment protects against myocardial ischemia/reperfusion injury via mediating lncRNA CASC15/miR-542-3p axis

Abstract

The protective effect of isoflurane on cardiomyocyte ischemia/reperfusion injury (I/RI) was explored in hypoxia and reoxygenation (H/R) induced cardiomyocyte injury model. In terms of mechanism, the participation of long non-coding RNA CASC15/microR-542-3p axis was further discussed. H9c2 cells received H/R treatment to mimic myocardial I/RI. RT-qPCR was performed to quantify mRNA levels. Cell viability and apoptosis were evaluated after isoflurane pretreatment and cell transfection. ELISA was performed to measure the concentrations of inflammatory/oxidative stress-related cytokines (TNF-α, IL-6, MDA, SOD). The target relationship between CASC12 and miR-542-3p was determined via dual-luciferase reporter assay. Isoflurane pretreatment alleviated H/R-induced cell viability suppression and cell apoptosis promotion, which was accompanied by CASC15 downregulation. CASC15 overexpression abolished the influence of isoflurane on cardiomyocytes’ viability and apoptosis. H/R-induced excessive release of TNF-α and IL-6 was hold down by isoflurane, which was re-activated after CASC15 overexpression. The concentration changes of both MDA and SOD by isoflurane were reversed by CASC15 overexpression. CASC15 functioned as miR-542-3p sponger, and miR-542-3p overexpression attenuated the effect of isoflurane and CASC15 on H/R-induced cardiac I/RI. Isoflurane pretreatment was beneficial for the alleviation of cardiac I/RI by inhibiting oxidative stress and myocardial inflammatory response. CASC15/miR-542-3p axis was required for isoflurane to exhibit its protective activity against cardiac I/RI.

Keywords:

• Cardiac I/RI
• isoflurane
• CASC15/miR-542-3p
• oxidative stress
• inflammatory response

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This article does not contain any studies with human participants or animals performed by any of the authors.

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All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

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