Gasdermin D Inhibitor Necrosulfonamide Alleviates Lipopolysaccharide/D-galactosamine-induced Acute Liver Failure in Mice  

作　　者：Yi-Long Wu Wei-Jie Ou Ming Zhong Su Lin Yue-Yong Zhu 

机构地区：[1]Endoscopy Center,the First Affiliated Hospital,Fujian Medical University,Fuzhou,Fujian,China [2]Department of Hepatol-ogy,Hepatology Research Institute,the First Affiliated Hospital,Fujian Medical University,Fuzhou,Fujian,China [3]Endocri-nology Department,Metabolic Diseases Research Institute,the First Affiliated Hospital,Fujian Medical University,Fuzhou,Fujian,China [4]Fujian Diabetes Research Institute,the First Affiliated Hospital,Fujian Medical University,Fuzhou,Fujian,China [5]Clinical Research Center for Liver and Intestinal Diseases of Fujian Province,Fuzhou,Fujian,China

出　　处：《Journal of Clinical and Translational Hepatology》2022年第6期1148-1154,共7页临床与转化肝病杂志（英文版）

基　　金：Fujian Province health education joint project(No.2019-WJ-16);Natural Science Foundation of Fujian Province(No.2021J01226);Startup Fund for scientific research,Fujian Medical University(2020QH1039).

摘　　要：Background and Aims:Acute liver failure(ALF)is as-sociated with high mortality.Gasdermin D(GSDMD)is the executioner of pyroptosis and is involved in the patho-physiology of immune dysregulation This study investi-gated the role of the GSDMD inhibitor necrosulfonamide(NSA)in ALF.Methods:An ALF model was established by lipopolysaccharide/D-galactosamine challenge in C57BL/6J mice.Mice were divided into four groups:normal controls(control group),ALF group(ALF group),dimethyl sulfoxide group(DMSO group),and NSA intervention group(NSA group).Survival was monitored,liver damage was de-termined by hematoxylin and eosin staining,and serum alanine aminotransferase(ALT).Underlying mechanisms were explored by quantitative real-time PCR,western blot-ting,and enzyme-linked immunosorbent assays.Results:Pyroptosis was activated in ALF model mice.Mice treat-ed with GSDMD inhibitor NSA developed less severe liver failure.NSA reduced the expression of GSDMD,NLRP3,cleaved caspase-1,cleaved caspase-11,and secretion of interleukin-1 beta in ALF mice model.Conclusions:Py-roptosis was activated in ALF.NSA alleviated ALF via the pyroptosis pathway.

关 键 词：Liver failure ACUTE PYROPTOSIS GSDMD GSDMD-NT Necrosul-fonamide 

分 类 号：R575.3[医药卫生—消化系统]