细胞铁死亡机制及其在肾脏疾病中的作用  

Mechanism of ferroptosis and its role in kidney diseases

作　　者：龚美玲 李俊华[1] Gong Mei-ling;Li Jun-hua(Department of Nephrology,Affiliated Tongji Hospital,Tongji Medical College,Huazhong University of Science&Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院肾病内科,武汉430030

出　　处：《临床肾脏病杂志》2021年第12期1028-1033,共6页Journal Of Clinical Nephrology

基　　金：国家自然科学基金(81470994,81100498)。

摘　　要：调节性细胞死亡(regulatory cell death, RCD)对于生物体的发育和维持体内平衡至关重要。以前,凋亡被认为是细胞死亡的唯一调控形式。然而,最近的研究表明RCD可以通过凋亡或几种非凋亡细胞死亡途径之一进行,包括最近描述的铁死亡(ferroptosis)和细胞焦亡(pyroptosis)等。铁死亡是在神经细胞损伤中发现的一种新的非凋亡性的细胞死亡形式,由细胞谷胱甘肽(glutathione, GSH)依赖性抗氧化防御系统的失活触发,导致脂质过氧化产物和反应性氧物质(reactive oxygen species, ROS)的毒性水平积累。最新的证据表明,铁死亡与多种肾脏疾病相关,包括急性肾损伤(acute kidney injury, AKI)、慢性肾脏疾病(chronic kidney disease, CKD)、多囊肾、肾细胞癌(renal cell carcinoma, RCC)等,研究发现可以通过激活或者抑制铁死亡来干预相关肾脏疾病的发展。本文就铁死亡的发现、特点、发生机制及其与肾脏疾病的关系展开论述,总结铁死亡的主要调控机制并梳理其与肾脏疾病的联系,为治疗肾脏疾病提供新的潜在靶点。Regulatory cell death(RCD) is essential for the development of organisms and the maintenance of homeostasis.Previously apoptosis was deemed as a sole form of RCD.However, recent studies have demonstrated that RCD could proceed through apoptosis or one of several non-apoptotic cell death pathways, including recently described ferroptosis and pyroptosis.Ferroptosis is a new form of cell death in nerve cell injury.Triggered by an inactivation of glutathione(GSH) dependent antioxidant defense system, it results in an accumulation of lipid peroxidation products and reactive oxygen species(ROS).The latest evidence has indicated that ferroptosis was correlated with acute kidney injury(AKI),chronic kidney disease(CKD),polycystic kidney disease and renal cell carcinoma(RCC),etc.And the development of related kidney disease could be intervened by activating or inhibiting ferroptosis.This review examined the discovery, characteristics and mechanism of ferroptosis and its relationship with kidney diseases, summarized the major regulatory mechanisms of ferroptosis and explained the relationship between ferroptosis and kidney disease to provide a new potential therapeutic target for kidney disease.

关 键 词：铁死亡 谷胱甘肽 谷胱甘肽过氧化物酶-4 铁代谢 肾脏疾病 

分 类 号：R692[医药卫生—泌尿科学]