Sevoflurane preconditioning attenuates myocardial cell damage caused by hypoxia and reoxygenation via regulating the NORAD/miR-144-3p axis.

Abstract

This study aimed to investigate the function and mechanism of lncRNA NORAD in Sevoflurane (Sev) protection against myocardial hypoxia-reoxygenation (H/R). Preprocess rat cardiomyocytes H9c2 cells with Sev at concentrations of 0.5%, 1.0%, and 1.5%, and subjected them to H/R treatment. qRT-PCR was used to detect levels of NORAD and miR-144-3p. Measure concentrations of the inflammatory cytokines IL-6, TNF-α, and IL-10, as well as cardiac injury markers cTnI, CK-MB, and LDH using ELISA. Assess cell proliferation and apoptosis using CCK-8 and flow cytometry. Perform dual-luciferase reporter assay and RIP assay to validate the targeting relationship between NORAD and miR-144-3p. H/R induced inhibition of cell proliferation, increase in apoptosis, and production of IL-6, TNF-α, CK-MB, LDH, and cTnI were significantly attenuated by Sev. As hypoxic treatment time lengthened, the NORAD levels in myocardial cells showed an increase, with Sev pretreatment being able to suppress the NORAD levels elevation. The overexpression of NORAD notably weakened the cardioprotective effect of Sev. NORAD targetedly binds to miR-144-3p and negatively regulates miR-144-3p. Increased miR-144-3p levels inhibited the antagonistic effect of NORAD on the cardioprotective effects of Sev. The current study confirmed that sevoflurane attenuated H/R-induced cardiomyocyte injury via the NORAD/miR-144-3p axis.