心肌梗死中铁死亡标志物研究进展

Advances in biological markers of ferroptosis in myocardial infarction

心肌梗死诊治进展使部分患者的预后获得明显改善,但患者的总体生存率仍不理想。深入研究心肌缺血再灌注后损伤机制可能改善研究的方向。铁死亡作为近年来新发现的调节性细胞死亡方式,其是主要由脂质过氧化引起的铁依赖性细胞死亡,特点是细胞死亡涉及脂质过氧化物和活性氧的积累。铁死亡被认为在缺血再灌注损伤中发挥重要作用。研究提示心肌梗死后的铁死亡相关标志物出现变化包括,细胞内铁代谢中的线粒体铁蛋白(mitochondrial ferritin,FtMt)缺失,谷胱甘肽代谢途径的末端分子谷胱甘肽过氧化物酶4(glutathione peroxidase 4,Gpx4)水平下降、谷胱甘肽合成中氨基酸逆向转运蛋白胱氨酸/谷氨酸转运体系统(cystine/glutamate transporter,System xc^(-),SXc^(-))功能下降和脂质代谢酶酰基辅酶A合成酶长链家族成员4(acyl-CoA synthetase long-chain family member 4,ACSL4)的过度表达,导致了心肌梗死后的氧化应激、炎症反应,加重心肌缺血再灌注损伤。FtMt、Gpx4、SXc^(-)和ACSL4这4种生物标志物是心肌梗死后铁死亡相关诊治的重要研究靶点,值得深入研究。

The development in diagnosis and treatment of myocardial infarction has significantly improved the prognosis of some patients,while the overall survival rate of patients remains much room for improvement.Further research of the mechanism of injury after myocardial ischemia and reperfusion may explore new directions of research.As a newly discovered form of regulated cell death,ferroptosis,an iron-dependent cell death caused by lipid peroxidation,which has been characterized by cell death involving the accumulation of lipid peroxides and reactive oxygen species.Ferroptosis,which has been acknowledged to play an important role in ischemia-reperfusion injury.Studies suggest that iron death-related marker changes after myocardial infarction(MI),including hiatus of mitochondrial ferritin(FtMt)in intracellular iron metabolism,decreased levels of glutathione peroxidase 4(Gpx4),a terminal molecule of glutathione metabolism pathway,insufficient use of antiporter cystine/glutathione synthesis(SXc^(-))in glutathione synthesis,and overexpression of Acyl-CoA synthetase long-chain family member 4(ACSL4)can lead to oxidative stress,inflammatory response,cardiomyocyte injury after myocardial infarction,and can aggravate the myocardial ischemia-reperfusion injury.The four biological markers mentioned above,FtMt,Gpx4,SXc^(-)and ACSL4,are important research targets for the diagnosis and treatment of iron death after MI,which may deserve further study.