Effect Of Lamivudine And Silymarin On TGF/Smads,CTGF,α-SMA In Liver Of HBV Transgenic Mice With Alcohol Drinking

ObjectiveTo investigate synergistic effects and molecular mechanism of hepatitis B virus (HBV) and alcohol on liver injury in HBV transgenic mice (HBV-Tg mice).Meanwhile,to investigate the protective effect and mechanism of Lamivudine (LMV) and Silymarin (SIL) on liver injury induced by alcohol drinking in HBV-Tg mice.MethodsThe one program of animal grouping:20 HBV-Tg mice and 20 wild-type mice were randomly divided into 4 groups:alcohol-fed Tg mice group (n=10) and alcohol-fed Wt mice group (n=10),were given intragastric administration with alcohol;control Tg mice group (n=10) and control Wt mice group (n=10),were received intragastric administration with saline.The other program of animal grouping:30 HBV-Tg mice were randomly divided into 3 groups:LMV group (n=10), HBV-Tg mice were given intragastric administration with alcohol,at the same time,were administrated intragastricly with LMV(100 mg/kg);SIL group (n=10),HBV-Tg mice were given intragastric administration with alcohol,at the same time,were administrated intragastricly with SIL(100 mg/kg);LMV+SIL group (n=10),HBV-Tg mice were given intragastric administration with alcohol,at the same time,were administrated intragastricly with LMV(100 mg/kg) and SIL(100 mg/kg).All groups were rasied for 10 weeks.The levels of HBV DNA copy number, ALT,AST in serum,the degree of inflammation,the degree of fibrosis,the mRNA expression of TGF-β1,Smad3,Smad7,CTGF and the protein expression of TGF-β1,CTGF,a-SMA in liver tissue were detected.All the staining figures were scanned with electronic computer and all the data were analyzed with SPSS 13.0 software.ResultsThe serum level of HBV DNA copies number,ALT and AST, the mRNA expression of TGF-β1,Smad3,Smad7,CTGF and the protein expression of TGF-β1,CTGF,a-SMA in liver all increased markedly in alcohol-fed Tg mice(vs control Tg mice,P<0.05).Alcohol consumption induced hepatocyte steatosis and hepatic inflammation in alcohol-fed Tg mice,but the change of liver fibrosis was not remarkable.Lamivudine and Silymarin single use respectively or drug combination failed to suppress the increased serum levels of HBV DNA copies number in alcohol-fed Tg mice.In alcohol-fed Tg mice,Silymarine single use or combined with Lamivudine could decrease the increased serum levels of ALT and AST(vs alcohol-fed Tg mice,P<0.05),but Lamivudine single use could not.Lamivudine and Silymarin single use respectively or drug combination could significantly relieve the histological injury and decrease the increased mRNA expression of TGF-β1,Smad3,CTGF and the protein expression of TGF-β1,CTGF,a-SMA mice(vs alcohol-fed Tg mice, P<0.05),but father improve the mRNA expression of Smad7(vs alcohol-fed Tg mice, P<0.05)in the liver.Conclusions1.Alcohol drinking have no effect on liver function, but enhancing the expression of TGF-β1,Smad3,Smad7, CTGF, a-SMA.2.HBV and alcohol have synergistic effects on early liver injury, by enhancing the expression of TGF-β1,Smad3,CTGF, inducing unbalanced expression of Smads and motivating the activation of HSC.3.Lamivudine and Silymarin single use respectively or drug combination could ruduce the serum level of ALT,AST;relieve the histological damage in the liver of alcohol-fed mice.The mechanism may be inhibiting the expression of TGF-β1,Smad3,CTGF,modulating the expression of Smads and suppressing the activation of HSC.