Role of farnesoid X receptor in rats with acute cholestatic hepatitis
10.3760/cma.j.issn.1007-3418.2016.06.009
- VernacularTitle:法尼醇X受体在大鼠急性淤胆型肝炎中的作用
- Author:
Yan DING
1
;
Xiaoli XIONG
;
Lei ZHAO
;
Huarong LI
Author Information
1. 430016,武汉市儿童医院内科
- Keywords:
Cholestasis;
Farnesoid X receptor;
Small heterodimer partner;
UDP-glucuronosyltransferases;
Bile salt export pump
- From:
Chinese Journal of Hepatology
2016;24(6):441-445
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of famesoid X receptor (FXR) and its downstream molecules small heterodimer partner (SHP),UDP-glucuronosyltransferase 2B4 (UGT2B4),and bile salt export pump (BSEP) in rats with acute cholestatic hepatitis.Methods A total of 20 Sprague-Dawley rats were randomly divided into normal control group and model group,with 10 rats in each group.The rats in the model group were given a single dose (50 mg/kg) of α-naphthyl isothiocyanate by gavage to establish the animal model of acute cholestatic hepatitis.Quantitative real-time PCR was used to measure the mRNA expression of FXR,UGT2B4,and BSEP in liver tissue at 48 hours after gavage.An automatic biochemical analyzer was used to measure the serum levels of total bilirubin,direct bilirubin,alanine aminotransferase,total bile acid,aspartate aminotransferase,alkaline phosphatase,and γ-glutamyl transferase.The independent samples t-test was used for comparison of means between groups.Results The model group had significantly lower mRNA expression of FXR,SHP,UGT2B4,and BSEP in liver tissue than the normal control group (0.152 ± 0.088/0.559 ±0.194/0.177 ± 0.039/0.561 ± 0.123 vs 1.137 ± 0.215/1.512 ± 0.309/2.394 ± 0.462/1.631 ± 0.376,t =13.408,8.260,15.121,and 8.553,all P ＜ 0.05).The model group had significantly higher liver fumction parameters than the normal control group (all P ＜ 0.01).Conclusion FXR,SHP,UGT2B4,and BSEP are involved in the development of acute cholestatic hepatitis.Reduced expression of FXR may cause reduced expression of downstream SHP,UGT2B4,and BSEP,increase the synthesis of bile acid,weaken detoxicating and transporting functions,and thus mediate the development of cholestatic hepatitis.
