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

发布时间：2018-03-31 09:25

  本文选题：酒精　切入点：HBV转基因小鼠　出处：《中南大学学报(医学版)》2017年03期

【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(P0.05)。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(P0.05),Smad7 mRNA的表达进一步增加(P0.05),水飞蓟素组血清ALT和AST水平降低(P0.05)。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。
[Abstract]:Aim: to observe the protective effect of lamivudine and silymarin on liver tissue of alcoholic hepatitis B virus hepatitis B virus (HBV) transgenic mice at the early stage of liver injury, and to explore the mechanism of liver fibrosis related factors.Methods: forty 1.3 copy HBV transgenic BALB/C mice were randomly divided into 4 groups.In the control group, normal saline was administered to the stomach.The model group was fed with 5 m L/kg of 50% volume fraction, the lamivudine group was given 100 mg / kg lamivudine solution on the basis of the model group, and the silymarin group was treated with silymarin solution on the basis of the model group.The serum HBV-DNA load of each group was measured by fluorescence quantitative PCR 10 weeks after intragastric administration of 200 mg 路kg ~ (-1) 路d ~ (-1).The levels of serum ALT and AST were detected by automatic biochemical instrument. The pathological changes of liver tissue were observed by HE staining and Masson staining. The expression of TGF- 尾 1, Smad3 Smad7, connective tissue growth factor- 鈪，

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