Alcohol Induced Liver Injury In HBV-Tg Mice And The Protctive Effects/Mechanism Of Silymarin And/or Lamivudine

Objective:To investigate the effects of alcohol on the liver function of HBV transgenic mice by detecting the HBV copy number,the levels of AST and ALT in the serum,the histological changes;the related mechanism were explored by detecting NF-κB,TGF-β1 mRNA and protein expression of NF-κB and TGF-β1 in the liver;And the therapentic effects of Lamivudine and/or Silymarin were observed.Method:Fifty HBV-transgenic mice and twenty wide type mice of the same germline were randomly divided into 7 groups,group A:wide type mice received intragastric administration with saline;group B:wide type mice received intragastric administration with alcohol;group C: HBV-transgenic mice received intragastric administration with saline; group D:HBV-transgenic mice received intragastric administration with alcohol;group E:HBV-transgenic mice received intragastric administration with alcohol and Lamivudine(100mg/kg bodyweight); group F:HBV-transgenic mice received intragastricadministration with alcohol,Lamivudine(100mg/kg bodyweight) and Silymarin(200mg/kg bodyweight);group G:HBV-transgenic mice received intragastric administration with Silymarin(200mg/kg bodyweight).All animals were killed at the end of the tenth week.The detection were done as follows:1. ALT,AST and HBV copies of serum were detected.2.The histological changes of the liver tissues were examined by pathological examination (HE staining);3.The mRNA and protein expression of NF-κB and TGF-β1 were detected by RT-PCR and immunohistochemistry respectively.Results:(1) In HBV-transgenic mice,the mRNA and protein expression of NF-κB,TGF-β1 were unregulated;However,there is no obvious pathological change in the liver.(2) Compared with HBV-transgenic control group,the serum levels of AST and ALT,the serum copy number of HBV,the mRNA and protein expression of NF-κB,TGF-β1 were increased markedly in HBV-transgenic mice treated with alcohol,much more inflammatory cells were gathered in the liver(P＜0.05 vs C group).(3) Lamivudine failed to suppress the increased serum levels of AST/ALT and HBV copies number in HBV-transgenic mice's caused by alcohol(P＞0.05 vs D group).However,Lamivudine decreased the mRNA levels of NF-κB, TGF-β1(P＜0.05 vs D group) without changing their protein expression (P＞0.05 vs D group).(4) Silymain depressed the increased AST,ALT levels,mRNA and protein expression of NF-κB an dTGF-β1(P＜0.05 vs D group),inflammatory cells in HBV-transgenic mice's liver caused by alcohol,but not HBV copies number and in HBV-transgenic mice's serum;(5)Lamivudine combined with Silymarin decreased the serum levels of AST and ALT,the mRNA and protein expression of NF-κB,TGF-β1(P＜0.05 vs D group),inflammatory cells in HBV-transgenic mice's liver caused by alcohol,and have tendency to decrease the increased HBV copies,but have no statistics difference(P＞0.05 vs D group).Conclusions:(1)Alcohol increases HBV copies number in HBV-transgenic mice and induces liver injury by enhancing the expression of NF-κB,TGF-β1.(2) Lamivudine could not inhibit the increased levels of AST,ALT and HBV-DNA copies in HBV-transgenic mice's serum caused by alcohol.(3) Silymarin or Silymarin combined with Lamivudine inhibits the increased levels of AST,ALT in the and inflammatory cells in the liver via decreasing the mRNA and protein expression of NF-κB and TGF-β1.