Effects of Combination Therapy of Rehin and Pioglitazone on Rats with Nonalcoholic Steatohepatitis

OBJECTIVE To elucidate effects of combination therapy of rehin and Pioglitazone on nonalcoholic steatohepatitis in rats with NASH and investigate the synergic mechanism of rehin and Pioglitazone on NASH. METHODS Totally 76 male SD rats were randomly divided into 6 groups after fed with normal diet for 7 days: Control group (n=14): fed with normal diet for 20 weeks (2 rats for 12 weeks and then executed); Model group (n=14): fed with high-fat and high-cholesterol diet consisting of the normal diet, 10% lard and 2% cholesterol, for 20 weeks (2 rats for 12 weeks and then were executed);Rhein group (n=12): Rhein was added orally after 12 weeks fed with high-fat and high-cholesterol diet;Pioglitazone group (n=12): Pioglitazone was added orally after 12 weeks fed with high-fat and high-cholesterol diet;combination group were divided into low-dose and high-dose group(n=12): different doses of Rhein and Pioglitazone were added orally after 12 weeks fed with high-fat and high-cholesterol diet. All the rats were executed after 20 weeks. Body mass, liver weight, transaminase level, blood glucose, triglyceride, cholesteral, insulin level and liver histology were detected. Serum insulin and tumor necrosis factor-a(TNF-a) level were measured by radio-immunity technique. The level of malondialdehyde (MDA), glutathione peroxidase (GSH-PX) was measured by chromatometry. RESULTS After 20 weeks, the model group developed lipid metabolic disorder and insulin resistance. Livers presented the pathology of severe hepatocyte steatosis and the sporadic inflammatory cell infiltration or focal necrosis. Lipid metabolic disorder and insulin resistance in intervention group were improved, along with the status of hepatocyte steatosis and inflammatory cell infiltration, compared with model group. Combination group was more effective than the single drug group. CONCLUSION Combination therapy of rehin and Pioglitazone can prevent the development of nonalcoholic steatohepatitis and is more effective than the single drug group. Combination group has obvious synergic therapeutic effect.