- Author:
Yueyong ZHU
1
;
Jiarong WU
;
Qi ZHENG
;
Jing DONG
;
Jiaji JIANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; Caspase 3; metabolism; Diet, High-Fat; Fenofibrate; pharmacology; Hepatocytes; drug effects; Non-alcoholic Fatty Liver Disease; pathology; Peroxisome Proliferator-Activated Receptors; metabolism; Proto-Oncogene Proteins c-bcl-2; metabolism; Rats; Rats, Sprague-Dawley; bcl-2-Associated X Protein; metabolism
- From: Chinese Journal of Hepatology 2015;23(9):688-693
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo use a rat model of nonalcoholic liver disease (NAFLD) to observe effects of the peroxisome proliferator-activated receptor-a (PPAR-a) agonist fenofibrate on hepatic steatosis in nonalcoholic fatty liver and to investigate the underlying mechanism.
METHODSSixty-six Sprague-Dawley rats were given adaptive feeding for 1 week and then randomly allocated into the following three groups: unmodeled control (group C,n =18), untreated NAFLD model (group M, n =24), and fenofibrate-treated NAFLD model (group F, n =24).Group C rats were given a normal diet, while group M and group F rats were given a high-fat diet. After model establishment, the group F rats were treated with fenofibrate (10 mg/kg/d, intraperitoneal) and the group C and group M rats were given sham-treatment with cosolvent (5 mL/kg/d, intraperitoneal). At the end of treatment weeks 4, 6 and 8, one-third of rats in each group were euthanized.Liver tissues were assessed by hematoxylin-eosin (HE) staining to determine level of steatosis and inflammaion activity, and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling to measure changes in hepatocyte apoptosis index. Changes in expression levels of the PPAR-a receptor and apoptosis factors (bcl-2, bax and caspase-3) were assessed by reverse transcription-PCR and immunohistochemistry.
RESULTSThe NAFLD modeled rats showed appropriate induction of hepatic steatosis, hepatic inflammation, and hepatocyte apoptosis. Compared to the group M rats, the group F rats showed lower expression of PPAR-and bcl-2 and higher expression of bax and caspase-3 at both the mRNA and protein level.
CONCLUSIONFenofibrate can ameliorate hepatic steatosis in an experimental rat model of NAFLD, and the mechanism may be associated with inhibition of hepatocyte apoptosis.