中国感染控制杂志2025，Vol.24Issue(6)：762-769,8.DOI:10.12138/j.issn.1671-9638.20256766
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
Hypoxia-inducible factor-1α inhibitor LW6 inhibits myocardial ferroptosis and ameliorates myocardial injury of sepsis in rats
摘要
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.关键词
缺氧诱导因子-1α/LW6/脓毒症/心肌病/铁死亡/SLC7A11/GPX4途径Key words
hypoxia-inducible factor-1α/LW6/sepsis/cardiomyopathy/ferroptosis/SLC7A11/GPX4 pathway分类
医药卫生引用本文复制引用
王晓悦,曾佑成,张艺馨,曹国栋,黄铭,林靓,杨鹏强,程青虹..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[J].中国感染控制杂志,2025,24(6):762-769,8.基金项目
国家自然科学基金项目(81860336、82060021) （81860336、82060021）
伊犁州临床医学研究院天山雪松名医培育项目(yl2023py04) （yl2023py04）
