NLRP3炎性小体活化与细胞焦亡在肝纤维化中的作用  

The NLRP3 inflammasome activation and pyroptosis in the liver fibrosis

作　　者：李珂云 陈水亲[1] 张婷 黄瑜涵 肖子庆 黄彬红[1] 张文娟[1,2] LI Ke-yun;CHEN Shui-qin;ZHANG Ting;HUANG Yu-han;XIAO Zi-qing;HUANG Bin-hong;ZHANG Wen-juan(School of Basic Medicine,Gannan Medical University;Key Laboratory of Ministry of Education for Prevention and treatment of Cardiovascular and Cerebrovascular Diseases,Gannan Medical University;The First Clinical Medical School of Gannan Medical University,Ganzhou,Jiangxi 341000)

机构地区：[1]赣南医学院基础医学院 [2]赣南医学院心脑血管疾病防治教育部重点实验室 [3]赣南医学院第一临床医学院,江西赣州341000

出　　处：《赣南医学院学报》2023年第7期739-745,共7页JOURNAL OF GANNAN MEDICAL UNIVERSITY

基　　金：心脑血管疾病防治教育部重点实验室开放课题(XN202016);赣南医学院博士启动基金(QD202111);江西省教育厅科学技术研究项目(GJJ211525,GJJ170872);江西省自然科学基金项目(20212BAB206003);江西省大学生创新创业训练项目(S202110413012,S202210413005);赣南医学院本科生科技创新项目(ZR2206,16)。

摘　　要：NLRP3炎性小体是由天然免疫受体蛋白NLRP3、衔接蛋白ASC和pro-Caspase-1组成的多蛋白复合体。NLRP3炎性小体活化后,pro-Caspase-1自活化为Caspase-1。Caspase-1一方面促使pro-IL-1β和pro-IL-18转变为IL-1β和IL-18,另一方面剪切gasdermin D(GSDMD)并释放N末端,形成Gasdermin D-NT。Gasdermin D-NT转移至细胞膜上,在细胞膜上形成孔道,将IL-1β和IL-18分泌至细胞外,同时细胞发生焦亡。此过程有助于抵抗病原体感染、应激反应,发挥天然免疫的防御作用并维持机体平衡状态。NLRP3炎性小体活化和细胞焦亡是肝纤维化发生发展的关键因素。肝纤维化形成中涉及多种细胞的NLRP3炎性小体活化和细胞焦亡过程,比如肝实质细胞、Kupffer细胞和肝星状细胞等。本文主要总结了NLRP3炎性小体的活化机制,并阐述了NLRP3炎性小体活化及细胞焦亡在肝纤维化中的作用。The NLRP3 inflammasome is a multi-protein complex composed of the innate immune receptor protein NLRP3,adaptor protein ASC and pro-Caspase-1.After the activation of NLRP3 inflammasome,pro-Caspase-1 was self-activated into Caspase-1.Caspase-1 promotes the transformation of pro-IL-1βand pro-IL-18 into IL-1βand IL-18,it also cuts gasdermin D(GSDMD)and releases the N-terminal to form Gasdermin D-NT.The Gasdermin D-NT is transferred to the cell membrane,formed pores on the cell membrane,and IL-1βand IL-18 are secreted out of the cell.At the same time,the pyroptosis occurs.This process helps to resist pathogen infection and induce inmmune response,so as to play the defensive role of innate immunity and maintain the balance of the body.The NLRP3 inflammasome activation and pyroptosis are key factors involved in the occurrence and progression of liver fibrosis.The NLRP3 inflammasome activation and pyroptosis are involved in the formation of liver fibrosis in a variety of cells,such as hepatocytes,kupffer cells,and hepatic stellate cells.This review discusses the activation mechanism of NLRP3 inflammasome,and summarizes the role of NLRP3 inflammasome activation and pyroptosis in the liver fibrosis.

关 键 词：肝纤维化 NLRP3炎性小体 细胞焦亡 肝实质细胞 KUPFFER细胞 

分 类 号：R392.9[医药卫生—免疫学]