[Effect of probucol in improving hepatic steatosis in rats with non-alcoholic steatohepatitis and the mechanism].
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).


CONCLUSIONS
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.
Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. E-mail: ycwr@sohu.com.
Rong
R
Wu
Xiaoling
X
Wu
Bo
B
Liu
Wei
W
Zhang
Jing
J
Gao
Xiaoqiu
X
Xiao
Xia
X
Zhang
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy*; D011341:Probucol / Q000494:pharmacology*; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley
D000924:Anticholesteremic Agents; D012333:RNA, Messenger; D011341:Probucol