Sevoflurane Preconditioning Mitigates Hypoxia and Reoxygenation Injury in Cardiomyocytes Through <scp>microRNA</scp> ‐451a Regulation

This study investigated whether Sevoflurane preconditioning (Sevo-pre) attenuates hypoxia/reoxygenation (H/R)-triggered myocardial damage by targeting microRNA-451a (miR-451a) and its downstream target interleukin 6 receptor (IL6R). Rat embryonic cardiomyoblast-derived H9C2 underwent H/R injury modeling with either Sevo-pre or no preconditioning. Mechanistic studies employed the manipulation of miR-451a overexpression and silencing, alongside IL6R modulation via targeted siRNA and plasmid transfection. Sevo-pre significantly enhanced cell viability, reduced apoptosis, and decreased injury markers in H/R-induced cells (p < 0.001). Notably, miR-451a was downregulated in H/R conditions but upregulated by Sevo-pre. The inhibition of miR-451a negated Sevo's protective effects, exacerbating oxidative stress and apoptosis (p < 0.001). Bioinformatics analyses and luciferase assays identified IL6R as a direct target of miR-451a. Silencing IL6R mitigated the adverse effects of miR-451a inhibition, restoring cell viability and reducing oxidative stress (p < 0.001). Sevo-pre alleviates H/R injury in cardiomyocytes through the regulation of miR-451a, which suppresses IL6R expression, consequently reducing oxidative stress and apoptosis. This study elucidates a novel cardioprotective mechanism of preconditioning via the miR-451a/IL6R axis, which highlights miR-451a and IL6R as potential therapeutic targets for mitigating myocardial I/R injury in clinical settings.