Huang Juanjuan, Liu Shikun, Li Zuojun, Cao Libo, Ouyang Linqi
Department of Pharmacy, First Hospital of Changsha, Changsha 410005; School of Pharmaceutical Science, Central South University, Changsha 410013, China.
School of Pharmaceutical Science, Central South University, Changsha 410013; Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2017 Mar 28;42(3):257-263. doi: 10.11817/j.issn.1672-7347.2017.03.004.
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.
观察拉米夫定和水飞蓟素对乙型肝炎病毒(HBV)转基因小鼠(Tg小鼠)酒精诱导的肝纤维化相关因子的防治作用。方法:将40只拷贝数为1.3的HBV-Tg BALB/C小鼠随机分为4组:对照组、模型组、拉米夫定组和水飞蓟素组。对照组Tg小鼠经胃内给予生理盐水;模型组Tg小鼠每天经胃内给予50%酒精(5 mL/kg);拉米夫定组和水飞蓟素组Tg小鼠分别每天经胃内给予酒精(5 mL/kg)加拉米夫定(100 mg/kg)和水飞蓟素(200 mg/kg)。所有组均饲养10周。检测血清中HBV-DNA拷贝数、ALT、AST水平,炎症程度、纤维化程度,肝组织中TGF-β1、Smad3、Smad7和结缔组织生长因子(CTGF)的mRNA表达水平,以及TGF-β1、CTGF和α-SMA的蛋白表达水平。所有图像用电子计算机扫描,数据用SPSS13.0软件分析。结果:与对照组相比,肝损伤明显加重,而HBV-DNA拷贝数、TGF-β1、Smad3、Smad7和CTGF的mRNA水平以及TGF-β1、CTGF和α-SMA的蛋白水平显著升高(P<0.05)。与模型组相比,水飞蓟素组和拉米夫定组肝损伤明显减轻,而TGF-β1、Smad3和CTGF的mRNA水平以及TGF-β1、CTGF和α-SMA的蛋白水平显著降低;Smad7的mRNA水平进一步升高(P<0.05);水飞蓟素组血清中ALT和AST水平降低(P<0.05)。结论:拉米夫定和水飞蓟素减轻了酒精喂养的Tg小鼠肝脏的组织学损伤。拉米夫定或水飞蓟素有益作用的机制可能与抑制TGF-β1、Smad3和CTGF的表达、调节Smads的表达以及抑制肝星状细胞的激活有关。