自噬在脓毒症急性肾损伤发病机制及治疗中的研究进展  

The advances on autophagy the pathogenesis and treatment in septic acute kidney injury

作　　者：田梓佑 张杰 聂诗琪 邓代花 李竹 唐立丽 李小悦 Tian Ziyou;Zhang Jie;Nie Shiqi;Deng Daihua;Li Zhu;Tang Lili;Li Xiaoyue(Department of Emergency,the Fifth Affiliated Hospital(Zhuhai)of Zunyi Medical University,Zhuhai 519100,Guangdong,China;Department of Intensive Care Medicine,the Fifth Affiliated Hospital(Zhuhai)of Zunyi Medical University,Zhuhai 519100,Guangdong,China)

机构地区：[1]遵义医科大学第五附属(珠海)医院急诊科,广东珠海519100 [2]遵义医科大学第五附属(珠海)医院重症医学科,广东珠海519100

出　　处：《中华危重病急救医学》2025年第2期183-187,共5页Chinese Critical Care Medicine

基　　金：国家自然科学基金(82460375,81960361)。

摘　　要：脓毒症是宿主对感染反应失调所致的致命性器官功能障碍综合征。脓毒症急性肾损伤(SAKI)是脓毒症较常见的并发症之一,急性肾损伤(AKI)的出现提示患者病情危重、预后不良。传统观点认为,SAKI的主要机制是脓毒症导致肾血流量减少、肾灌注不足、炎症反应、微循环障碍,进而导致肾小管细胞缺血和坏死。最新的研究结果表明,自噬等程序性细胞死亡发挥着日益重要的作用。自噬是一种程序化细胞内降解过程,属于程序性细胞死亡。细胞通过溶酶体降解自身胞质成分,将胞内组分拆解回收,实现细胞自身代谢需要,维持细胞内环境稳态及细胞器更新。自噬在SAKI期间通过调控炎症和免疫反应,清理损伤的细胞器,以及维持细胞内环境稳定等多方面发挥重要保护作用。近年来,自噬在SAKI发病机制及治疗中的作用受到广泛关注。研究证实,多种靶向自噬的细胞内信号通路和分子,如哺乳动物雷帕霉素靶蛋白(mTOR)信号通路、腺苷酸活化蛋白激酶(AMPK)信号通路、核转录因子-κB(NF-κB)信号通路,以及去乙酰化酶(SIRT)、自噬相关因子Beclin-1、Toll样受体(TLR)参与SAKI的发生发展。由于SAKI发病机制复杂,目前SAKI的治疗方案包括液体管理、抗感染、维持内环境平衡和肾脏替代治疗等,但病死率仍居高不下。近年已发现自噬在脓毒症介导的AKI中具有关键的细胞保护作用,并且有越来越多的药物可通过调控自噬缓解SAKI。本文针对自噬在SAKI发病机制及治疗中的最新进展进行综述,以期为SAKI患者的新药研发提供见解。Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection.Septic acute kidney injury(SAKI)is one of the most common complications of sepsis,and the occurrence of acute kidney injury(AKI)indicates that the patient's condition is critical with a poor prognosis.The traditional view holds that the main mechanism of SAKI is the reduction of renal blood flow,inadequate renal perfusion,inflammatory response,and microcirculatory dysfunction caused by sepsis,which subsequently leads to ischemia and necrosis of renal tubular cells.Recent research findings indicate that processes such as autophagy and other forms of programmed cell death play an increasingly important role.Autophagy is a programmed intracellular degradation process and is a form of programmed cell death.Cells degrade their cytoplasmic components via lysosomes,breaking down and recycling intracellular constituents to meet their metabolic needs,maintain intracellular homeostasis,and renew organelles.During SAKI,autophagy plays a crucial protective role through various mechanisms,including regulating inflammation and immune responses,clearing damaged organelles,and maintaining stability in the intracellular environment.In recent years,the role of autophagy in the pathogenesis and treatment of SAKI has received widespread attention.Research has confirmed that various intracellular signaling pathways and signaling molecules targeting autophagy[such as mammalian target of rapamycin(mTOR)signaling pathway,AMP-activated protein kinase(AMPK)signaling pathway,nuclear factor-κB(NF-κB)signaling pathway,and Sirtuins(SIRT),autophagy associated factor Beclin-1,and Toll-like receptor(TLR)]are involved in the development of SAKI.Due to the complex pathogenesis of SAKI,current treatment strategies include fluid management,infection control,maintenance of internal environment balance,and renal replacement therapy;however,the mortality remains high.In recent years,it has been found that autophagy plays a critical protective r

关 键 词：自噬 脓毒症 脓毒症急性肾损伤 发病机制 治疗 

分 类 号：R692[医药卫生—泌尿科学] R459.7[医药卫生—外科学]