Study On The Protective Effect And Related Mechanisms Of Rosiglitazone On The Acute Hepatic Failure In Mice

Objective:To explore the possible mechanism that D-galactosamine (D-GaIN)and lipopolysaccharide(LPS)induced the acute hepatic failure in mice;To observe the protective effect of Rosiglitazone in the acute hepatic failure of mice which induced by D-GalN and LPS,and explore the possible mechanism.Methods:①D-GaIN 600mg/Kg and LPS 10ug/Kg was injected into abdominal cavity which administered the acute hepatic failure model of the mice.Rosiglitazone 20mg/kg body weight was lavaged for the therapy.②60 male mice were divided into three groups randomly(the normal group,the control group,the therapy group),the control group and the therapy group were given D-GalN/LPS injection,while the normal group was injected by saline;the therapy group was lavaged by Rosiglitazone 20mg/kg body weight at 2 hours before the D-GalN/LPS injection,while the control group and the normal group was lavaged by saline.Compare the 24 hours survival rate,the serum level of ALT/AST, and the histopathological changes of the liver.The level of TNF-α,TGF-β1 and Caspase-3 mRNA of the liver were simultaneously measured by semiquantitative RT-PCR.Result:①we succeeded in administering the acute hepatic failure model by intraperitoneal injection of D-GaIN 600mg/Kg combined with LPS 10ug/Kg:The 24 hours survival rate was 20%;The serum level of ALT, AST was significantly increased,P＜0.05;Massive necrosis of hepatocellular parenchyma were observed histologically.The level of TNF-α,TGF-β1 and Caspase-3 mRNA of the liver was significantly higher than the normal group,P＜0.05.②Compare the control group to the therapy group:a.The 24 hours survival rate of the therapy group was significantly higher than the control group,60%VS 20%,P＜0.05.b.The serum levels of ALT in the therapy group were significantly lower than the control group,403.6±76.1 U/L VS 3664.8±646.1 U/L, P＜0.05;The serum levels of AST in the therapy group were significantly lower than the control group,464.6±63.0 U/L VS 3514.0±468.9 U/L, P＜0.05.c.The degree of liver injury in the therapy group were significantly reduced than the control group.d.The levels of TNF-αmRNA in the hepatic tissue of the therapy group were lower significantly than the control group,0.270±0.042 VS 0.459±0.072,P＜0.05;The levels of TGF-β1 mRNA in the hepatic tissue of the therapy group were lower significantly than the control group, 0.261±0.031 VS 0.403±0.042,P＜0.05;The levels ofCaspase-3 mRNA in the hepatic tissue of the therapy group were lower significantly than the control group,0.388±0.033 VS 0.553±0.033,P＜0.05.Conclusion:(1)Succeeded in administering the acute hepatic failure model of mice by intraperitoneal injection of D-GalN 600mg/Kg combined with LPS 10ug/Kg,the possible mechanism was that D-GalN/LPS increased the expression of TNF-α,TGF-β1 and Caspase-3.(2)Rosiglitazone play an effectively protective role in the acute hepatic failure of mice.Rosiglitazone can inhibit the inflammation of liver,decrease the necrosis;Rosiglitazone can decrease the mortality of the acute hepatic failure.The possible mechanism was that rosiglitazone reduced the expression of TNF-α,TGF-β1 and Caspase-3.