Effects Of Piglitazone On Liver Fibrosis In Rats With Non-Alcoholic Steatohepatitis

Aims To detect the effects and the potential mechanism of piglitazone on liverfibrosis in rats with non-alcoholic steatohepatitis.Methods Forty male Sprague-Dawley (SD) rats, after being fed normal chow for one week, and then randomly divided into four groups:(1) normal control group (NC group, n=10) were maintained on the standard chow and lavaged with normal saline,(2) high fat diet group (HD group, n=10) were maintained on the high fat diet (HFD) and lavaged with normal saline,(3) pioglitazone control group (NP group, n=10) were maintained on the standard chow and lavaged with pioglitazone (10mg/kg per day),(4) pioglitazone intervention group (HP group, n=10) were maintained on the HFD and lavaged with pioglitazone. After24weeks of treatment with pioglitazone, we evaluated changes in body weight, liver weight, ratio of liver/body weight, liver histology, serum concentrations of alanine aminotransferase (ALT), aspartate aminotransaminase (AST), free fatty acid (FFA), triglyceride (TG), fasting blood glucose (FBG), fasting blood insulin (FINS), homeostatic model assessment insulin resistance (HOMA-IR), transforming growth factor (TGF)-β1and adiponectin, and as well as liver adiponectin mRNA, phosphorylated AMP-activated protein kinase (p-AMPK), a-smooth muscle actin (a-SMA) and collagen I expression.Results The degree of body weight, liver weight, ratio of liver/body weight, NAS, fibrosis, serum concentration of ALT, FFA, TG, FBG, FINS, HOMA-IR, TGF-β1, liver a-SMA and collagen I protein expression were significantly higher (p<0.05) in HD group than in NC group. Serum adiponectin concentration, and liver adiponectin mRNA and p-AMPK protein expression were significantly lower (p<0.05) in HD group than in NC group. Compared with NC group, serum concentration of TG was significantly lower (p<0.05), serum concentration of FBG and liver p-AMPK protein expression were significantly higher (p<0.05), but no significant effect on others. Pioglitazone significantly reduced the degree of liver weight, ratio of liver/body weight, NAS, fibrosis, serum concentration of ALT, FFA, TG, FBG, FINS, HOMA-IR, TGF-β1, liver a-SMA and collagen I protein expression (p<0.05). Pioglitazone significantly raised serum adiponectin concentration, liver adiponectin mRNA and p-AMPK protein expression (p<0.05). But had no effect on body weight (p>0.05). Serum concentration of AST was no significantly effect in all group (p>0.05).Conclusion (1) In rats with high fat-induced NASH, treatment with piglitazone can improve insulin resistance and liver steatosis.(2) piglitazone can decrease extracellular matrix in liver, improve liver fibrosis.(3) piglitazone can increase serum concentration of adiponectin, increase the expression of adiponectin and p-AMPK in liver.(4) It is possible that piglitazone improve liver fibrosis through the upregulation of adiponectin and p-AMPK.