Xiao Chenggen, Li Xiangmin
Department of Emergency, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024 Aug 28;49(8):1333-1340. doi: 10.11817/j.issn.1672-7347.2024.240233.
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.
细胞焦亡是一种由炎性半胱天冬酶触发的程序性细胞死亡形式，依赖于gasdermin（GSDM）家族蛋白在质膜上形成膜孔，GSDM蛋白作为细胞焦亡的执行者。该过程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（SA-AKI）是一种没有特异性治疗药物的典型炎症性疾病。研究强调了细胞焦亡在SA-AKI发病和进展中的作用，但受细胞焦亡影响的具体肾细胞群体以及详细的调控机制仍不清楚。细胞焦亡可能与SA-AKI密切相关，目前调节细胞焦亡的策略集中在靶向炎性小体、关键半胱天冬酶、GSDM蛋白和下游炎症因子。尽管这些策略仍存在一些脱靶效应或副作用，但它们为脓毒症靶向治疗的研究提供了基础，并阐明了未来的研究方向以及此类研究的必要性。
