Dysregulation of bile acid signal transduction causes neurological dysfunction in cirrhosis rats  

作　　者：Chao Ren Li Cha Shu-Yue Huang Guo-Hui Bai Jin-Hui Li Xin Xiong Yu-Xing Feng Dui-Ping Feng Long Gao Jin-Yu Li 

机构地区：[1]College of Medical Imaging,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China [2]Department of Ultrasound,Qingdao Central Hospital,University of Health and Rehabilitation,Qingdao 266000,Shandong Province,China [3]Academy of Medical Sciences,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China [4]Department of Occupational Health,School of Public Health,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China [5]Department of Oncological and Vascular Intervention,First Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi Province,China

出　　处：《World Journal of Hepatology》2025年第3期140-151,共12页世界肝病学杂志(英文)

基　　金：Supported by the National Natural Science Foundation of China,No.82200650;the Key Research and Development Projects of Shanxi Province,No.202102130501014;the Natural Science Foundation of Shanxi Province,No.202203021211021,No.202203021212046,and No.20210302123258.

摘　　要：BACKGROUND The pathogenesis of hepatic encephalopathy(HE)remains unclear,and the classical theory of ammonia toxicity lacks sufficient justification.AIM To investigate the potential of bile acids as intervention targets for HE.METHODS This study employed 42 wild-type male SD rats weighing 200±20 g.Using a random number table method,two rats were randomly selected to undergo common bile duct ligation(BDL).The remaining 40 rats were randomly assigned to four groups serving as controls:The vehicle+control diet(VC)group,the thioacetamide(TAA)group,the TAA+total bile acids(TAAT)group,and the TAA+cholestyramine(TAAC)group.Except for the VC group,all rats were intraperitoneally injected with 100 mg/kg TAA solution once daily for ten consecutive days to establish a HE model.Simultaneously,the TAAT and TAAC groups were administered a diet containing 0.3%bile acids(derived from BDL rats)and 2%cholestyramine,respectively,by gavage for ten days.For the BDL rat model group,the common BDL procedure was performed following the aforementioned protocol.After four weeks,laparotomy revealed swollen bile ducts at the ligation site,and bile was collected.Following successful modeling,behavioral tests,including the elevated plus maze and open field test,were conducted to assess the HE status of the rats.Peripheral blood,liver,and cerebral cortex tissue samples were collected,and the total bile acid content in the serum and cerebral cortex was measured using an enzyme cycling method.The levels of inflammatory factors in the serum and cerebral cortex were analyzed using enzyme-linked immunosorbent assay.Liver histological examination was performed using the hematoxylin-eosin double-labeling method.Reverse transcription polymerase chain reaction,western blot,immunohistochemistry,and other techniques were employed to observe the expression of microglial activation marker ionized calcium-binding adaptor molecule-1 and Takeda G protein-coupled receptor 5(TGR5)protein.RESULTS Compared to the VC group,the TAA group exhibited an exacerbation

关 键 词：Hepatic encephalopathy Total bile acid THIOACETAMIDE G protein-coupled bile acid receptor 1 Liver cirrhosis 

分 类 号：R57[医药卫生—消化系统]