上海交通大学学报（医学版）2025，Vol.45Issue(12)：1559-1567,9.DOI:10.3969/j.issn.1674-8115.2025.12.001
血红蛋白诱导心肌细胞铁死亡及Basigin的调控机制研究
Mechanisms of Basigin regulation in hemoglobin-induced cardiomyocyte ferroptosis
摘要
Abstract
Objective·To investigate the mechanism of hemoglobin(Hb)-induced cardiomyocyte injury and the regulatory role of Basigin(BSG)in this process.Methods·An in vitro model was established by treating H9c2 cardiomyocytes with different concentrations of Hb(0,7.5,15.0,and 30.0 μmol/L);cell viability and mortality were detected using the WST-1 assay and flow cytometry.Subsequently,H9c2 cardiomyocytes underwent hypoxia/reoxygenation treatment with low-concentration gradients of Hb(0,2.5,5.0,and 7.5 μmol/L)to simulate the pathological microenvironment of ischemia-reperfusion injury,further validating Hb's toxic effects on cardiomyocytes.Multiple cell death inhibitors were used,including a necroptosis inhibitor(necrostatin-1,Nec-1),an autophagy inhibitor(3-methyladenine,3-MA),a ferroptosis inhibitor(ferrostatin-1,Fer-1),and a pyroptosis inhibitor(VX-765),to investigate the mechanism of Hb-induced cardiomyocyte injury.Bsg mRNA and protein levels were detected by Western blotting and real-time quantitative PCR.Bsg expression was knocked down in H9c2 cardiomyocytes using siRNA;the role of BSG in Hb-induced cardiomyocyte injury and ferroptosis was then verified by the WST-1 assay and flow cytometry.Results·Under both normoxic and hypoxia/reoxygenation conditions,Hb showed direct toxic effects on H9c2 cardiomyocytes in a concentration-dependent manner.Further investigation showed that,compared with other cell death inhibitors,the ferroptosis inhibitor Fer-1 more significantly alleviated Hb-induced cardiomyocyte injury.Western blotting and real-time quantitative PCR results demonstrated that compared with the control group,Bsg mRNA and protein expression levels were significantly increased in Hb-treated H9c2 cardiomyocytes.Knockdown of Bsg expression decreased the mRNA expression of the ferroptosis marker prostaglandin-endoperoxide synthase 2(Ptgs2)and alleviated Hb-induced cardiomyocyte injury and death.Conclusion·Hb may induce myocardial injury by promoting cardiomyocyte ferroptosis;BSG plays a role in this process,and inhibition of its expression can counteract Hb-induced ferroptosis and cardiomyocyte injury.关键词
心肌内出血/缺血再灌注损伤/血红蛋白/心肌细胞/铁死亡/BasiginKey words
intramyocardial hemorrhage/ischemia-reperfusion injury/hemoglobin(Hb)/cardiomyocyte/ferroptosis/Basigin(BSG)分类
医药卫生引用本文复制引用
李文丽,钟方元,赵怡超,金力行,雷杰,石瑶,卜军,葛恒..血红蛋白诱导心肌细胞铁死亡及Basigin的调控机制研究[J].上海交通大学学报（医学版）,2025,45(12):1559-1567,9.基金项目
国家自然科学基金(81770238) （81770238）
新疆维吾尔自治区自然科学基金(2022D01C16) （2022D01C16）
上海市卫生健康委员会学科带头人计划(2022XD018). National Natural Science Foundation of China(81770238) （2022XD018）
Natural Science Foundation of Xinjiang Uygur Autonomous Region(2022D01C16) （2022D01C16）
Discipline Leader Program of Shanghai Municipal Health Commission(2022XD018). （2022XD018）
