TLR4 Knockout Attenuates BDL-induced Liver Cholestatic Injury through Amino Acid and Choline Metabolic Pathways  

作　　者：Shou-hua ZHANG Meng-jie YU Jin-long YAN Ju-hua XIAO Yu XIAO Jia-le YANG Jun LEI Xin YU Wei-long CHEN Yong CHAI 

机构地区：[1]Department of General Surgery,Jiangxi Provincial Children's Hospital,Nanchang 330006,China [2]Key Laboratory of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China [3]Department of General Surgery,Second Affiliated Hospital of Nanchang University,Nanchang 330006,China [4]Department of Ultrasound,Jiangxi Provincial Maternal and Child Health Hospital,Nanchang 330006,China [5]department of Ophthalmology,Jiangxi Provincial Children's Hospital,Nanchang 330006,China

出　　处：《Current Medical Science》2021年第3期572-580,共9页当代医学科学（英文）

基　　金：the National Natural Science Foundation of China(Nos.81960101,81860483).

摘　　要：The exact mechanism by which knockout of Toll-like receptor 4(TLR4)attenuates the liver injury remains unclear.The present study aimed to examine the role of TLR4 in the pathogenesis of bile duct ligation(BDL)-induced liver cholestatic injury and the underlying mechanism.Wild type(WT)mice and TLR4 knockout(TLR4-KO)mice were used for the establishment of the BDL model.Metabolomics were applied to analyze the changes of small molecular metabolites in the serum and liver of the two groups.The serum biochemical indexes and the HE staining results of liver tissue showed that liver damage was significantly reduced in TLR4-KO mice after BDL when compared with that in WT mice.The metabolite analysis results showed that TLR4 KO could maintain the metabolisms of amino acids-and choline-related metabolites.After BDL,the amino acids-and choline-related metabolites,especially choline and 3-hydroxybutyrate,were significantly increased in WT mice(both in serum and liver),but these metabolites in the liver of TLR4-KO mice after BLD were not significant different from those before BLD.In conclusion,TLR4 KO could attenuate BDL-induced liver cholestatic injury through regulating amino acid and choline metabolic pathways.

关 键 词：Toll-like receptor 4 biliary obstruction metabolomics LIVER bile duct ligation 

分 类 号：R57[医药卫生—消化系统]