细胞焦亡在糖尿病肾脏疾病中的作用机制及研究进展

Mechanism of action and research progress of pyroptosis in diabetic kidney disease

细胞焦亡主要表现为细胞肿胀,形成缺乏离子选择性的孔隙,引起“焦亡小体”样泡状突起,最终造成质膜裂解,释放炎症因子。细胞焦亡主要由炎性半胱天冬酶(cysteinylaspartate specific proteinase,caspase)介导,包括由caspase-1介导的经典焦亡途径和caspase-4/5/11介导的非经典焦亡途径,通过触发下游的消皮素D(gasdermin,GSDMD),引起细胞膜穿孔,从而释放细胞内容物和大量的炎性细胞因子,诱发细胞焦亡。近年来,越来越多的证据表明细胞焦亡参与糖尿病肾脏疾病(diabetic kidney disease,DKD)疾病进展,可能成为DKD的潜在治疗靶点。本文将对细胞焦亡在DKD疾病进展的相关研究进行综述,总结现阶段肾脏固有细胞焦亡在DKD发病机制中的作用及靶向细胞焦亡的相关药物研究,以期为DKD疾病机制研究与治疗策略的更新提供新的思路。

Cell pyroptosis is characterized by cellular swelling and the formation of ion non-selective pores,leading to the emergence of“pyroptotic body-like”vesicular protrusions,ultimately resulting in plasma membrane lysis and the release of inflammatory factors.Cell pyroptosis is mainly mediated by inflammatory cysteinyl aspartate specific proteinase(caspase),including the classical pyroptotic pathway mediated by caspase-1 and the non-classical pyroptotic pathway mediated by caspase-4/5/11.This process triggers downstream gasdermin to cause cell membrane perforation,thus leading to the release of cellular contents and numbers of inflammatory cytokines and inducing cell pyroptosis.In recent years,increasing evidence suggests that cell pyroptosis is involved in the progression of diabetic kidney disease(DKD)and may serve as a potential therapeutic target for DKD.This article provides a review of the relevant research on cell pyroptosis in the progression of DKD and summarizes the current understanding of the role of intrinsic renal cell pyroptosis in the pathogenesis of DKD and drug studies targeting cell pyroptosis,aiming to offer new insights for updating research on the mechanisms and treatment strategies of DKD.