Protective effects of rosiglitazone on non-alcoholic steatohepatitis in rats / 中华临床营养杂志

ABSTRACT

ObjectiveTo investigate the preventive effects of rosiglitazone on nonalcoholic steatohepatitis (NASH) rats and to explore the potential mechanisms in modulating peroxisome proliferator-activated receptor gamma (PPARγ),nuclear factor kappa B (NF-κB),and cyclooxygenase-2 (COX-2) expression.Methods Thirty male SD rats were assigned into the normal group ( n =10),the model group ( n =10),rosiglitazone prevention group [ n =10,simultaneously 4mg/( kg · d) gavage daily at beginning].Liver appearance,liver index,and histological changes were assessed.Serum tumor necrosis factor-o (TNF-c) and prostaglandin E2 (PGE2) were determined using enzyme-linked immunosorbent assay.The expressions of PPARγ,NF-κB,and COX-2 in liver were determined using immunohistochemical methods.The mRNA and protein expressions of COX-2 were disclosed by real-time polymerase chain reaction and Western blot analysis.ResultsCompared with the normal group,the liver index significantly increased in model group (3.92 ±0.72 vs.5.71 ± 1.05,P =0.004).HE and Masson staining showed significantly increased steatosis,inflammation,and fibrosis.The serum levels of TNF-α,PGE2 in high-fat-diet-fed rats were significantly increased ( 11.72 ± 2.47 vs.29.39 ± 5.32,P =0.002 ; 236.60 ± 24.90vs.288.24 ± 17.17,P =0.004).Immunohistochemistry showed NF-κB and COX-2 in livers were significantly elevated,but PPARγ wasdecreased in nonalcoholic steatohepatitis rats.Real-time polymerase chain reaction and Western blot found mRNA and protein expressions of COX-2 were increased in the model group (0.57 ± 0.08 vs.2.83 ± 0.24,P =0.0007 ; 0.38 ± 0.03 vs.1.00 ± 0.03,P =0.004).Compared with the model group,the expressions of PPARγsignificantly increased and the expressions of NF-κB and COX-2 significantly decreased ( mRNA2.83 ± 0.24 vs.0.46 ± 0.11,P =0.002 ; protein 1.00 ± 0.03 vs.0.62 ± 0.02,P =0.006 ) in the rosiglitazone prevention group.ConclusionBy inhibiting NF-κB and COX-2 expressions,rosiglitazone can reduce insulin resistance and then prevent the occurrence and deve lopment of nonalcoholic steatohepatitis.