title: [Effects of fenofibrate on hepatocyte apoptosis in nonalcoholic fatty liver].
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  Sixty-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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Fenofibrate can ameliorate hepatic steatosis in an experimental rat model of NAFLD, and the mechanism may be associated with inhibition of hepatocyte apoptosis.
authors.affiliation: Liver Research Center, First Affiliated Hospital of Fuijian Medical University, Fuzhou 350005, China.
authors.forename: Yueyong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jiarong
authors.initials: J
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Jiaji
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D059305:Diet, High-Fat; D011345:Fenofibrate / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects*; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D047492:Peroxisome Proliferator-Activated Receptors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3; D011345:Fenofibrate