细胞焦亡与脓毒症相关急性肾损伤  

Pyroptosis and sepsis-associated acute kidney injury

作　　者：肖成根 李湘民[1] XIAO Chenggen;LI Xiangmin(Department of Emergency,Xiangya Hospital,Central South University,Changsha 410008,China)

机构地区：[1]中南大学湘雅医院急诊科,长沙410008

出　　处：《中南大学学报（医学版）》2024年第8期1333-1340,共8页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(82202424);中国博士后基金面上项目(2022M713534)。

摘　　要：细胞焦亡是一种由炎性半胱氨酸蛋白酶介导的依赖于消皮素(gasdermin,GSDM)家族蛋白在质膜上形成膜孔后触发炎症的程序性死亡方式,GSDM蛋白是细胞焦亡的执行蛋白。细胞焦亡可通过级联效应激活强烈的炎症反应。脓毒症相关急性肾损伤(sepsis-associated acute kidney injury,SA-AKI)是一种经典的炎症性疾病,尚无明确的特效治疗药物。目前,有关细胞焦亡参与SA-AKI发生和发展的研究已有论述,但细胞焦亡作用于肾脏的具体细胞群及调控机制尚未明晰。细胞焦亡可能与SA-AKI关系密切,目前调控细胞焦亡的策略多集中在靶向炎症小体、Caspase关键酶、GSDM蛋白以及下游炎症因子等方面。虽然这些策略仍会存在一些脱靶效应或不良反应,但其为脓毒症靶向药物的研究奠定了基础,也明确了未来研究的方向和必要性。Pyroptosis is a form of programmed cell death triggered by inflammatory caspases,dependent on the gasdermin(GSDM)family proteins forming membrane pores in the plasma membrane,with GSDM proteins serving as the executors of pyroptosis.This process can activate a robust inflammatory response through a cascade effect.Sepsis associated acute kidney injury(SA-AKI)is a classical inflammatory disease with no specific therapeutic drug available.Studies have highlighted the role of pyroptosis in the onset and progression of SA-AKI,yet the specific renal cell populations affected by pyroptosis and the detailed regulatory mechanisms remain unclear.Pyroptosis may be closely related to SA-AKI,with current strategies for regulating pyroptosis focusing on targeting inflammasomes,key caspase enzymes,GSDM proteins,and downstream inflammatory factors.Although these strategies still present some off-target effects or side effects,they provide a foundation for research into sepsis-targeted therapies and clarify future research directions and the necessity of such studies.

关 键 词：细胞焦亡 脓毒症相关急性肾损伤 GSDM蛋白 程序性细胞死亡 脂多糖 

分 类 号：R459.7[医药卫生—急诊医学] R692[医药卫生—治疗学]