坏死性凋亡在慢性肾脏病中的作用机制进展  

Research progress on role of necroptosis in chronic kidney disease

作　　者：邱萍 黄朔 骆启晗 马青 陈傅喆 单子怡 刘一鸣 李昌煜[2] QIU Ping;HUANG Shuo;LUO Qi-han;MA Qing;CHEN Fu-zhe;SHAN Zi-yi;LIU Yi-ming;LI Chang-yu(School of Basic Medical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China;School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China;the First School of Clinical Medicine,Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学基础医学院,浙江杭州310053 [2]浙江中医药大学药学院,浙江杭州310053 [3]浙江中医药大学第一临床医学院,浙江杭州310053

出　　处：《中国药理学通报》2025年第5期816-820,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82074304,82003830);浙江中医药大学校级科研基金(No 2021JKZKTS016B);“尖兵”“领雁”研发攻关计划项目(No 2023C03004)。

摘　　要：慢性肾脏病(chronic kidney disease,CKD)是以肾脏结构损伤和功能障碍为主要特征的慢性疾病。目前,临床上尚缺乏针对CKD有效的治疗药物和防治手段。越来越多的研究证明,坏死性凋亡作为一种新型程序性细胞死亡方式,在CKD的发病及病程进展中扮演着至关重要的角色。针对坏死性凋亡途径的关键分子,如RIPK1、RIPK3和MLKL,开发小分子抑制剂已成为治疗CKD的新兴策略,已在多种体内外模型中展现出明显的保护肾脏和缓解肾纤维化潜力。该文总结了近年来坏死性凋亡机制的研究进展,并重点阐述了坏死性凋亡在CKD发病机制中的潜在作用以及靶向该途径的治疗潜力,为未来CKD的防治提供新的视角和研究方向。Chronic kidney disease(CKD)is a chronic disease characterized by renal structural damage and dysfunction.At present,there is still a lack of effective therapeutic drugs and prevention and treatment methods for CKD in clinical practice.More and more studies have shown that necroptosis,as a new type of programmed cell death,plays a vital role in the onset and progression of CKD.Targeting key molecules in the necroptosis pathway,such as RIPK1,RIPK3 and MLKL,the development of small molecule inhibitors has become an emerging strategy for the treatment of CKD,and has shown significant potential to protect the kidneys and alleviate renal fibrosis in a variety of in vitro and in vivo models.Therefore,this article summarizes the research progress of the mechanism of necroptosis in recent years,and focuses on the potential role of necroptosis in the pathogenesis of CKD and the therapeutic potential of targeting this pathway,providing a new perspective and research direction for the prevention and treatment of CKD in the future.

关 键 词：坏死性凋亡 慢性肾脏病 肾纤维化 RIPK1 小分子抑制剂 MLKL 

分 类 号：R322.61[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学] R692