Hypoxia-inducible factor-1α inhibitor LW6 inhibits myocardial ferroptosis and ameliorates myocardial injury of sepsis in rats
10.12138/j.issn.1671-9638.20256766
- VernacularTitle:缺氧诱导因子-1α抑制剂LW6抑制心肌铁死亡改善大鼠脓毒症心肌损伤
- Author:
Xiaoyue WANG
1
;
Youcheng ZENG
;
Yixin ZHANG
;
Guodong CAO
;
Ming HUANG
;
Liang LIN
;
Pengqiang YANG
;
Qinghong CHENG
Author Information
1. 石河子大学第一附属医院重症医学二科,新疆石河子 832000;石河子大学医学院,新疆石河子 832000
- Publication Type:Journal Article
- Keywords:
hypoxia-inducible factor-1α;
LW6;
sepsis;
cardiomyopathy;
ferroptosis;
SLC7A11/GPX4 pathway
- From:
Chinese Journal of Infection Control
2025;24(6):762-769
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of hypoxia-inducible factor-1α(HIF-1α)inhibitor LW6 on ferroptosis in septic cardiomyopathy rats.Methods Rat septic cardiomyopathy model was prepared using cecal ligation and puncture(CLP)method.Thirty-six specific pathogen-free(SPF)6-8 weeks male SD rats were randomly divided into the sham-operated group,CLP group,CLP+solvent group,LW6 group,ferrostatin-1(Fer-1)group,and LW6+Fer-1 group.The degree of myocardial damage in each group was evaluated through hematoxylin-eosin stai-ning and detection of lactate dehydrogenase and creatine kinase content in cardiac tissue.Myocardial mitochondrial damage was observed by transmission electron microscopy.Ferroptosis level was determined by detecting iron ion concentration,reduced glutathione,malondialdehyde,and reactive oxygen species.Protein expression levels of HIF-1α,solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4)in cardiac tissue were detected by Western blotting.Results Compared with the CLP group and the CLP+solvent group,the LW6 group could ameliorate myocardial damage,alleviate mitochondrial damage,inhibit ferroptosis-related indicators(all P＜0.05),reduce HIF-1α protein expression levels(P＜0.05),and enhance SLC7A11 and GPX4 protein expression levels(both P＜0.05).Conclusion LW6 decreases HIF-1α expression and ferroptosis levels through the SLC7A11/GPX4 pathway,and ameliorates sepsis-induced cardiomyopathy.
