细胞焦亡在炎症性肠病中的研究进展

Study insights into inflammatory bowel disease through pyroptosis

炎症性肠病(inflammatory bowel disease,IBD)是由遗传和环境因素共同作用导致肠道黏膜的慢性炎症,随着对IBD发病机制研究的不断深入,目前研究显示细胞焦亡可能参与IBD的发生发展。细胞焦亡是细胞程序性死亡的重要组成部分,是细胞内病原体感染引起的炎症反应。半胱氨酸天冬氨酸特异性蛋白酶(cysteinyl aspartate specific protease,Caspase)激活后诱导细胞焦亡的发生,根据Caspase在细胞程序性死亡中所起的作用,分为依赖Caspase-1的经典途径和依赖Caspase-4/5/11的非经典途径。焦亡相关的Caspase活化后可造成包括GSDMD在内的多种Gasdermin家族成员发生剪切和多聚化,造成细胞膜孔洞形成,引起细胞渗透性死亡。细胞焦亡可能是未来IBD治疗的潜在靶点,本文阐述细胞焦亡的发生机制及以细胞焦亡为靶点的IBD治疗策略。

Inflammatory bowel disease(IBD)is characterized by chronic relapsing intestinal inflammation which caused by genetic and environmental factors.With the research on the pathogenesis of IBD,current studies show that pyroptosis may be involved in the development of IBD.As an essential part of programmed cell death,pyroptosis is an inflammatory response that is elicited upon infection by intracellular pathogens.Activated inflammatory caspases will induce pyroptosis.According to the role of Caspase in programmed cell death,it can be divided into Caspase-1-dependent canonical pathway and Caspase-4/5/11-dependent non-canonical pathway.Activated inflammatory caspases cleave the pore-forming effector protein,gasdermin-D,inducing osmotic pressure deregulation of internal fluids and subsequently rupturing the cell membranes.Pyroptosis may be a potential therapeutic target for IBD in the future.This review described the mechanism of pyroptosis and therapeutic strategies for IBD.