Effect of probucol in improving hepatic steatosis in rats with non- alcoholic steatohepatitis and the mechanism
10.3969/j.issn.1673-4254.2014.05.29
- VernacularTitle:降脂药普罗布考改善NASH大鼠肝脏脂肪变性的机制
- Author:
Rong WU
1
;
Xiaoling WU
;
Bo LIU
;
Wei ZHANG
;
Jing GAO
;
Xiaoqiu XIAO
;
Xia ZHANG
Author Information
1. 重庆医科大学附属第二医院消化内科
- Keywords:
non-alcoholic steatohepatitis;
probucol;
farnesoid X receptor;
SREBP-1C
- From:
Journal of Southern Medical University
2014;(5):731-735
- CountryChina
- Language:Chinese
-
Abstract:
Objective To determine the effects of probucol on serum parameters and liver histopathology in rats with non-alcoholic steatohepatitis (NASH) and explore the mechanisms. Methods Forty male Sprague-Dawley rats were randomly assigned into 4 equal groups, namely the normal control group (NC group) with a standard feeding, high-fat diet group (HD group) fed with a high-fat diet, probucol (500 mg/kg daily) control group (NP group) fed with standard diet, and probucol group fed with a high-fat diet (HP group). After 15 weeks of feeding, the rats were euthanized for histopathological inspection of the liver with HE staining and detection of farnesoid X receptor (FXR), SHP and SREBP-1C expressions using semi-quantitative RT-PCR and Western blotting. Results After the 15-week feeding, the rats in HP group had significantly lower levels of serum ALT, AST, cholesterol, bile acid, and free fatty acid than those in HD group (P<0.01 or 0.05). Compared with the normal control group, high-fat diet feeding resulted in significantly decreased mRNA and protein levels of FXR and SHP (P<0.05) and significantly increased SREBP-1C level (P<0.05). These high-fat diet-induced gene expression changes were reversed by probucol intervention (P<0.05). Conclusion Probucol treatment has beneficial effects on serum parameters, hepatic steatosis, and lobular inflammation in high-fat diet-induced NASH possibly by up-regulating FXR expression.