Role of hepatic bile acids on altered synthesis and transport in the pathogenesis of colitis-related cholestasis in rats
10.13699/j.cnki.1001-6821.2017.18.015
- VernacularTitle:肝胆汁酸合成及转运异常在大鼠结肠炎性胆汁淤积发病中的作用
- Author:
Xiao ZUO
1
;
Fang-Fang LIU
;
Tian-Xue GUO
;
Zhi RAO
;
Yu-Hui WEI
;
Hong-Yan QIN
;
Xin-An WU
Author Information
1. 兰州大学第一医院药剂科
- Keywords:
ulcerative colitis;
cholestasis;
cholesterol 7α-hydroxylase;
multidrug resistance-associated protein 2
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(18):1785-1788
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of bile acids on altered synthesis and transport in the pathogenesis of colitis-related cholestasis and the underlying mechanisms in rats.Methods Adult Wistar male rats were randomly divided into normal group and model group,ulcerative colitis(UC) model was established by administration 2,4,6-trinitro-benzenesulfonicacid in intro-colonic,while rats in normal group were colonic administered with saline.UC model was evaluated by calculating disease activity index,histopathological score and myeloperoxidase activity.Serum level of alkaline phosphatase (ALP),glutamyl transpeptidase (GGT),alanine aminotransferase (ALT) and aspartate aminotransferase(AST) were also determined.Moreover,the level of hepatic total bile acids,deoxycholic acid and lithocholic acid were determined by HPLC/MS.The hepatic protein expression of bile acids synthesis enzyme cholesterol 7α-hydroxylase(Cyp7a1) as well as bile acids export transporter multidrug resistance-associated protein 2 (Mrp2) were all investigated by Western-bolt.Results Compared to the normal group,disease activity index,histopathological score and myeloperoxidase activity in model group were all significantly increased to (4.51 ± 1.49),(1.36 ± 0.69) point,and (0.40 ± 0.07) U · mg-1,respectively (all P ＜ 0.05),suggesting the successful preparation of UC rat model.Compared to the normal group,the content of total bile acids and deoxycholic acid were all markedly increased to (85.50 ± 18.60) μmol · L-1 and (1.50 ± 0.68) ng · g-1 in model group,and the serum level of ALP and GGT were all significantly increased to (259.43 ±58.58) U · L-1and (1.50 ±0.68) U · L-1 in model group (all P ＜ 0.05),indicating the occurrence of cholestasis in model group of rats.Compared to the normal group,the protein expression of Cyp7a1 in the liver of model group was significantly increased to 0.72 ± 0.07 in gray value,but the protein expression of Mrp2 was markedly decreased to 0.66 ± 0.04 in gray value in model group (all P ＜ 0.05).Conclusion Acute colitis can induce intrahepatic cholestasis in rats,increased bile acids synthesis and decreased bile acids excretion may contribute to colitis-related cholestasis via up-regulating Cyp7a1 expression and down-regulating Mrp2 expression in the liver of colitis rats.
