The effect of rosiglitazone in modulating cyclooxygenases-2 in nonalcoholic steatohepatitis rats / 中华消化杂志

ABSTRACT

Objective To evaluate the impact of rosiglitazone (Ros) on liver expression of peroxisome proliferator-activated receptor γ (PPARγ),nuclear factor (NF-κB) and cyclooxygenase-2(COX-2) in treatment of nonalcoholic steatohepatitis (NASH) rats.Methods Thirty Sprague-Dawley rats were divided into normal group,model group and Ros treated group with 10 each.Except the normal group,the other two groups were given high fat diet for 12 weeks for NASH model.The rats in Ros treated group were gavaged 4 mg/kg of Ros daily at the 12th week for 8 weeks.All rats were sacrificed at the 20th week for blood sample and liver tissue.Biochemical parameters of liver function,lipid metabolism,glycometabolism and antioxidant enzyme activities were measured.The histological change of the liver were assessed with HE and Masson staining.The level of tumor necrosis factor (TNF)-α and prostaglandin E2 (PGE2) was measured using ELISA.The expression of PPARγ,NF-κB and COX-2 was detected with immunohistochemistry.The mRNA and protein expressions of COX-2 were tested by real-time PCR and Western blotting,respectively.Results In comparison with model group,Ros treated group showed significant improvement in hepatic steatosis,inflammation and fibrosis(all P value<0.05).In model group,the serum levels of fasting blood glucose,insulin and HOMA-insulin resistance index (HOMA-IRI),total cholesterol (TC),total triglyeride (TG),lowdensity lipoprotein cholesterol (LDL-C) and free fatty acids were increased,but HDL-C level was decreased.All above parameters markedly improved after Ros treatment.The levels of ALT and AST,total anti-oxidation competence,superoxide dismutase,catalase,glutathione peroxidase and malondialdehyde in Ros treated group were significantly ameliorated when compared with those in model group.Immunohistochemistry showed that the expression of NF-κB and COX-2 was significantly elevated,but PPARγ was decreased in model group.Real-time PCR and Western blot revealed that the mRNA and protein expressions of COX-2 were higher in the model group than those in normal group (0.57±0.08 vs 0.38±0.03;2.83±0.24 vs 1.00±0.03,P=0.000 and P=0.004,respectively),but significantly lower in Ros treated group (0.55±0.06 and 1.84±0.13,P<0.01).Conclusions Ros can reduce oxidative stress and insulin resistance in NASH rats by activing PPARγ expression and inhibiting expression of NF-κB and cyclooxygenases.