GSDMD介导的肝细胞焦亡在急性肝衰竭中的致病机制

Pathogenesis of GSDMD-mediated pyroptosis of hepatocytes in acute liver failure

消皮素D(gasdermin D,GSDMD)是一种广泛表达的蛋白质,可以被肝细胞内的炎性因子激活。一旦被激活,GSDMD的N末端域(GSDMD-N)将形成孔道,导致细胞膜破裂和胞浆泄漏,最终导致细胞死亡。细胞焦亡是GSDMD介导的最具特征的致炎性裂解细胞死亡模式。最近研究发现,GSDMD被激活可扩大炎症反应,诱导肝细胞焦亡,进而加快急性肝衰竭的进展。本文着重探讨了GSDMD介导的肝细胞焦亡在急性肝衰竭中的致病机制及潜在的治疗靶点,以期为寻找有效治疗急性肝衰竭的潜在干预靶点提供新思路。

Gasdermin D(GSDMD)is a widely expressed protein that can be activated by inflammatory factors within hepatocytes.Once activated,the N-terminal domain of GSDMD(GSDMD-N)will form pores,leading to rupture of cell membranes and leakage of cytoplasm,ultimately leading to cell death.Pyrozosis is the most characteristic mode of inflammatory lytic cell death mediated by GSDMD.Recent studies have found that activation of GSDMD amplifies the inflammatory response and induces pyrosis of liver cells,thereby accelerating the progression of acute liver failure.This article focuses on the pathogenic mechanism and potential therapeutic targets of GSDMD-mediated hepatocyte pyrozosis in acute liver failure,in order to provide new ideas for finding potential intervention targets for the effective treatment of acute liver failure.