Sevoflurane Alleviates Myocardial Ischemia-Reperfusion Injury via the HMGB1/ACSL4 Pathway to Suppress Ferroptosis.

摘要

Sevoflurane (sevo) exhibits cardioprotective effects against myocardial ischemia/reperfusion injury (MIRI); however, its precise molecular mechanism of action remains elusive and warrants further in-depth investigation. A rat model of MIRI and a hypoxia/reoxygenation (H/R) model in the H9c2 cardiomyocytes were established separately, followed by sevo treatment. Hematoxylin-eosin staining, Perls staining, transmission electron microscope, FerroOrange staining, and Liperfluo staining were used to assess myocardial pathological damage, iron deposition, and oxidative stress. The contents of malondialdehyde, glutathione, Fe2+, and NADP + /NADPH were examined via relevant kits. Western blot, co-immunoprecipitation, and immunofluorescence staining assays were employed to verify the interaction between high mobility group box 1 (HMGB1) and acyl-CoA synthetase long chain family member 4 (ACSL4). In the rat MIRI model, sevo treatment mitigated myocardial tissue damage, attenuated oxidative stress, suppressed Fe2+ accumulation, and downregulated the expression of HMGB1 and ACSL4. In the H9c2 cardiomyocyte H/R injury model, sevo treatment enhanced cell viability, reduced intracellular Fe2+ levels, and alleviated lipid peroxidation. HMGB1 interacted with ACSL4 to stabilize ACSL4 protein expression. Furthermore, HMGB1 overexpression promoted H/R-induced injury and ferroptosis in cardiomyocytes, whereas sevo abrogated these effects. Sevo alleviates MIRI and H/R injury by suppressing the HMGB1/ACSL4 pathway to mitigate ferroptosis, providing a new theoretical basis for myocardial protection approaches.