Related Experiment Video
Updated: Aug 11, 2026
Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
Sevoflurane Alleviates Myocardial Ischemia-Reperfusion Injury via the HMGB1/ACSL4 Pathway to Suppress Ferroptosis
Yuliu Mei1, Yunfei Cao1, Cheng Sheng1
1Department of Anesthesiology, Beilun Branch of the First Affiliated Hospital, College of Medicine, Zhejiang University, Ningbo, Zhejiang, China.
Abstract:
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.
Insights
Sevoflurane protects the heart by inhibiting the HMGB1/ACSL4 pathway, reducing iron-dependent cell death (ferroptosis) and mitigating damage from heart attacks and oxygen deprivation.
Area of Science:
- Cardiology
- Anesthesiology
- Cell Biology
Background:
- Sevoflurane (sevo) offers cardioprotection against myocardial ischemia/reperfusion injury (MIRI).
- The exact molecular mechanisms underlying sevoflurane's protective effects are not fully understood.
- Investigating these mechanisms is crucial for developing improved therapeutic strategies.
Purpose of the Study:
- To elucidate the molecular mechanism by which sevoflurane alleviates myocardial ischemia/reperfusion injury (MIRI).
- To investigate the role of the high mobility group box 1 (HMGB1) and acyl-CoA synthetase long chain family member 4 (ACSL4) pathway in sevoflurane-mediated cardioprotection.
- To determine if sevoflurane mitigates ferroptosis in the context of MIRI and hypoxia/reoxygenation (H/R) injury.
Main Methods:
- Established rat MIRI and H9c2 cardiomyocyte H/R models.
- Utilized histological staining (H&E, Perls, FerroOrange, Liperfluo) and biochemical assays to assess damage, iron deposition, and oxidative stress.
- Employed Western blot, co-immunoprecipitation, and immunofluorescence to analyze protein interactions and expression, focusing on HMGB1 and ACSL4.
Main Results:
- Sevoflurane treatment reduced myocardial damage, oxidative stress, and iron accumulation in the MIRI rat model.
- Sevoflurane enhanced H9c2 cell viability, decreased intracellular iron, and alleviated lipid peroxidation in the H/R model.
- Sevoflurane suppressed the interaction and expression of HMGB1 and ACSL4, thereby inhibiting ferroptosis and mitigating H/R-induced injury.
Conclusions:
- Sevoflurane alleviates MIRI and H/R injury by suppressing the HMGB1/ACSL4 pathway.
- This suppression mitigates ferroptosis, offering a novel mechanism for sevoflurane's cardioprotective effects.
- The findings provide a new theoretical basis for myocardial protection strategies utilizing sevoflurane.
