title: [Effect of lamivudine and silymarin on liver fibrosis-relevant factors in HBV transgenic mice with alcohol drinking].
abstract: To observe the role of lamividine and silymarin preventing and curing liver fibrosis-relevant factors induced by alcohol drinking in hepatitis B virus (HBV) transgenic mice (Tg mice).  Methods: Forty HBV-Tg BALB/C mice with 1.3 copy were randomly divided into 4 groups: a control group, a model group, a lamivudine group and a silymarin group. Tg mice in control group were treated with normal saline via intragastric administration; Tg-mice in the model group were treated with 50% alcohol (5 mL/kg) once a day via intragastric administration; while Tg-mice in lamivudine group and silymarin group were treated with alcohol (5 mL/kg) plus laminvudine (100 mg/kg) and silymarin (200 mg/kg) once a day via intragastric administration respectively. All groups were raised 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 levels of TGF-β1, Smad3, Smad7 and connective tissue growth factor (CTGF), and the protein expression levels of TGF-β1, CTGF and α-SMA in liver tissue were detected. All the images were scanned with electronic computer and the data were analyzed with SPSS13.0 software.  Results: Compared with the control group, liver injury were significantly aggravated, while HBV-DNA copies, mRNA levels of TGF-β1, Smad3, Smad7 and CTGF as well as the protein levels of TGF-β1, CTGF and α-SMA were significantly increased (P<0.05). Compared with the model group, liver injury were significantly attenuated in silymarine group and lamivudine group, while mRNA levels of TGF-β1, Smad3 and CTGF as well as the protein levels of TGF-β1, CTGF and α-SMA were significantly decreased; mRNA level of Smad7 was further increased (P<0.05); the levels of ALT and AST in serum were decreased in the silymarine group (P<0.05).  Conclusion: Lamivudine and silymarin relieve the histological damage in the liver of alcohol-fed Tg mice. The mechanisms for the beneficial effects of lamivudine or silymarin might be related to inhibiting the expression of TGF-β1, Smad3 and CTGF, modulating the expression of Smads and suppressing the activation of HSC.
authors.affiliation: Department of Pharmacy, First Hospital of Changsha, Changsha 410005; School of Pharmaceutical Science, Central South University, Changsha 410013, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Science, Central South University, Changsha 410013; Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Shikun
authors.initials: S
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Science, Central South University, Changsha 410013; Department of Pharmacy, Th ird Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Zuojun
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science, Central South University, Changsha 410013, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Cao
authors.affiliation: School of Pharmaceutical Science, Central South University, Changsha 410013, China.
authors.forename: Linqi
authors.initials: L
authors.lastname: Ouyang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004279:DNA, Viral / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics*; D019259:Lamivudine / Q000627:therapeutic use*; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D020011:Protective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D012838:Silymarin / Q000627:therapeutic use*; D051900:Smad3 Protein / Q000097:blood; D051906:Smad7 Protein / Q000097:blood; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D020011:Protective Agents; D012838:Silymarin; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D019259:Lamivudine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase