铁死亡及其在糖尿病肾脏疾病肾小管损伤中的作用  

Ferroptosis and its role in kidney tubular injury in diabetic kidney disease

作　　者：李子依 王俭勤[1,2] Li Ziyi;Wang Jianqini(Department of Nephrology,the Second Clinical Medical School of Lanzhou University,Lanzhou 730030,China;Department of Nephrology,the Second Hospital of Lanzhou University,Lanzhou 730030,China)

机构地区：[1]兰州大学第二临床医学院肾内科,兰州730030 [2]兰州大学第二医院肾内科,兰州730030

出　　处：《中华肾脏病杂志》2025年第2期144-153,共10页Chinese Journal of Nephrology

基　　金：甘肃省创新基地和人才计划(21JR7RA436);甘肃省高等学校创新基金(2022B-050);兰州市人才创新创业项目(2021-RC-94);兰州大学第二医院“萃英科技创新”计划(CY2021-QN-B01)。

摘　　要：铁死亡是一种以铁依赖性脂质活性氧积累为特征的程序性细胞死亡,与细胞内氨基酸、脂质和铁的代谢密切相关,调节铁死亡可干预和治疗某些疾病.糖尿病肾脏疾病(diabetic kidney disease,DKD)为糖尿病慢性微血管并发症,DKD的发病机制尚不清楚,现有的研究结果证实铁死亡参与了 DKD的发生和发展,尤其在糖尿病肾小管损伤中发挥了重要作用,抑制铁死亡可能为DKD治疗的一个方向.近年来,研究者通过DKD动物模型对铁死亡进行了大量研究,但有关铁死亡的具体发病机制及治疗效果尚未被完全揭示.该文综述了铁死亡及其与细胞凋亡、自噬等不同形式细胞死亡的联系;谷氨酸-胱氨酸反向转运体-谷胱甘肽-谷胱甘肽过氧化物酶4(系统Xc-GSH-GPX4)轴、烟酰胺腺嘌呤二核苷酸磷酸-铁死亡抑制蛋白1-辅酶Q10(NADPH-FSP1-CoQ10)轴、GTP环化水解酶1-四氢生物蝶呤-磷脂(GCH1-BH4-磷脂)轴和多种调节因子调控铁死亡的机制;铁死亡在DKD肾小管损伤中的作用等.通过这些内容的综述,探讨铁死亡作为DKD治疗靶点的可能性,以期为DKD的基础研究和临床治疗提供参考.Ferroptosis is a type of programmed cell death characterised by iron-dependent accumulation of lipid reactive oxygen species,which is closely related to intracellular metabolism of amino acids,lipids,and iron,and regulation of ferroptosis can intervene and treat certain diseases.Diabetic kidney disease(DKD)is a chronic microvascular complication of diabetes.Although the exact pathogenesis of DKD is not clear,the results of the existing studies have proved that ferroptosis participates in the development of diabetic kidney injury,and plays an important role in kidney tubular injury in particular,and the inhibition of ferroptosis may be one of the directions for the treatment of DKD.In recent years,researchers have conducted a lot of studies on ferroptosis through animal models of DKD,but the specific pathogenesis and therapeutic effects regarding ferroptosis have not been fully revealed.This article introduces ferroptosis and its connection with apoptosis,autophagy and other forms of cell death,as well as the main mechanisms regulating the development of ferroptosis through systematic Xc-GSH-GPX4 axis,NADPH-FSP1-CoQ10 axis,GCH1-BH4-phospholipid axis and various regulatory factors,and provides an overview of its role in kidney tubular injury of DKD.Through the review of these contents,the possibility of ferroptosis as a therapeutic target for DKD is discussed,in order to provide reference for the basic research and clinical treatment of DKD.

关 键 词：铁死亡 米糖尿病肾病 肾小管 月脂质过氧化作用 铁代谢 

分 类 号：R587.2[医药卫生—内分泌]