拉米夫定和水飞蓟素对酒精刺激的HBV转基因小鼠肝纤维化相关因子的影响  

Effect of lamivudine and silymarin on liver fibrosis-relevant factors in HBV transgenic mice with alcohol drinking

作　　者：黄娟娟[1,2] 刘世坤[2,3] 李佐军[2,3] 曹力波[2] 欧阳林旗[2] 

机构地区：[1]长沙市第一医院药剂科,长沙410005 [2]中南大学药学院,长沙410013 [3]中南大学湘雅三医院药学部,长沙410013

出　　处：《中南大学学报（医学版）》2017年第3期257-263,共7页Journal of Central South University ：Medical Science

摘　　要：目的:观察在肝损伤早期,拉米夫定和水飞蓟素对酒精刺激的乙型肝炎病毒(hepatitis B virus,HBV)转基因小鼠肝组织保护作用,并通过检测肝纤维化相关因子探讨其机制。方法:将40只1.3拷贝HBV转基因BALB/C小鼠随机分为4组。对照组以生理盐水灌胃;模型组以体积分数为50%的白酒5 m L/kg灌胃,1次/d;拉米夫定组在模型组处理基础上以拉米夫定溶液(100 mg/kg)灌胃,1次/d;水飞蓟素组在模型组处理基础上以水飞蓟素溶液(200 mg/kg)灌胃,1次/d。10周后荧光定量PCR检测各组小鼠血清HBV-DNA载量,全自动生化仪检测血清ALT和AST水平。HE染色,Masson染色镜检观察肝组织病理变化,荧光实时定量PCR检测肝组织TGF-β1,Smad3,Smad7,结缔组织生长因子(connective tissue growth factor,CTGF)mRNA表达水平,免疫组织化学检测肝组织TGF-β1,CTGF,α-平滑肌肌动蛋白(α-SMA)表达水平。结果:与对照组相比,模型组肝组织病理损伤加重,血清HBV病毒载量,ALT和AST水平明显增高,肝组织内TGF-β1,Smad3,Smad7,CTGF mRNA及TGF-β1,CTGF,α-SMA蛋白表达增加(P<0.05)。与模型组相比,拉米夫定组和水飞蓟素组肝组织病理损伤均减轻,肝组织内TGF-β1,Smad3,CTGF mRNA及TGF-β1,CTGF,α-SMA蛋白表达减少(P<0.05),Smad7 mRNA的表达进一步增加(P<0.05),水飞蓟素组血清ALT和AST水平降低(P<0.05)。结论:拉米夫定和水飞蓟素可通过调节TGF-β1/Smads信号通路,减少CTGF表达,抑制肝星状细胞活化等机制阻断酒精刺激的HBV转基因小鼠肝组织纤维化的发生和进展。Objective： To observe the role of lamividine and silymarin preventing and curing liver fibrosisrelevant 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

关 键 词：酒精 HBV转基因小鼠 拉米夫定 水飞蓟素 TGF-Β1/SMAD 结缔组织生长因子 α-平滑肌肌动蛋白 

分 类 号：R575.2[医药卫生—消化系统] R512.62[医药卫生—内科学]