Sevoflurane alleviates hypoxia/reoxygenation-induced cardiomyocyte injury via the LINC00173/miR-490-3p/MAPK1 axis

Myocardial cell injury is the central pathological link of various cardiovascular diseases. Sevoflurane (Sevo) possesses myocardial protective effects, but the underlying molecular mechanisms, particularly the long non-coding RNA (lncRNA)-mediated regulatory network, remain to be further elucidated, especially regarding LINC00173. Therefore, t his study investigated the role of the LINC00173/miR-490-3p/MAPK1 axis in the cardioprotective effect of Sevo against hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury, aiming to elucidate this axis as a potential novel target for Sevo against myocardial ischemia-reperfusion injury. H9c2 rat cardiomyocytes were subjected to H/R injury with Sevo post-conditioning. Quantitative real-time PCR (qRT-PCR), Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), and Western blot were performed to assess gene expression, cell viability, injury markers, inflammatory cytokines, oxidative stress indicators, and apoptosis-related proteins. Dual-luciferase reporter assays verified targeting relationships. H/R injury significantly upregulated the expression of LINC00173 and MAPK1, while downregulating miR-490-3p expression, and these effects were reversed by Sevo post-conditioning. Dual-luciferase reporter assays confirmed the direct targeting relationships between LINC00173 and miR-490-3p, as well as between miR-490-3p and MAPK1. Functional experiments showed that LINC00173 overexpression partially reversed the protective effect of Sevo on cardiomyocyte viability and exacerbated cell injury and apoptosis, whereas miR-490-3p overexpression reversed the detrimental effects induced by LINC00173. Furthermore, MAPK1 knockdown significantly reversed the cell damage caused by miR-490-3p inhibition. Sevo alleviates H/R-induced cardiomyocyte injury and apoptosis through the LINC00173/miR-490-3p/MAPK1 regulatory axis, wherein Sevo downregulates LINC00173 expression, relieves LINC00173-mediated sponging inhibition of miR-490-3p, and consequently suppresses MAPK1 expression.