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目的:验证肝细胞生长因子(HGF)基因治疗在胆管结扎肝纤维化中的保护作用。方法:用雄性CD-1小鼠,随机分为3组。正常对照组仅解剖肝门分离胆总管,不作胆管结扎;胆管结扎的2组,分别给予HGF质粒(pCMV-HGF,1μg/g)和空质粒(pcDNA3),每2周1次。3个月后将小鼠处死,评价肝纤维化程度。结果:肝细胞生长因子基因治疗能显著减少胆管周围胶原的沉积,表现在:肝胶原染色(Masson-Trichrome染色)减少;胆管周围Ⅰ型和Ⅲ型胶原的免疫荧光染色减少。和空质粒组相比,HGF治疗组肝组织羟脯氨酸的含量显著降低(两组分别为0.48±0.04μg/mgvs1.37±0.06μg/mg,P<0.05);肝纤维母细胞的激活减少——表现为肝组织中α-SMA的表达减少(两组分别为0.32±0.05vs.0.84±0.14,P<0.05);TGF-β1的表达减少(两组分别为0.69±0.11vs.1.31±0.23,P(0.01)。结论:在胆管结扎肝纤维化中,肝细胞生长因子基因治疗能减轻肝纤维化的程度,肝细胞生长因子可用于肝纤维化的治疗。
Objective: To verify the protective effect of hepatocyte growth factor (HGF) gene therapy on hepatic fibrosis induced by bile duct ligation. Methods: Male CD-1 mice were randomly divided into three groups. The normal control group only anatomized the common bile duct in the hepatic portal without biliary ligation. Two groups of bile duct ligation were given HGF plasmid (pCMV-HGF, 1μg / g) and empty plasmid (pcDNA3) once every two weeks. Mice were sacrificed after 3 months to assess the degree of liver fibrosis. Results: Hepatocyte growth factor gene therapy can significantly reduce the deposition of collagen around the bile ducts. The results are as follows: reduced by Masson-Trichrome staining; reduced immunofluorescence staining of type I and type III collagen around the bile duct. Compared with the empty plasmid group, the content of hydroxyproline in liver tissue of HGF treatment group was significantly decreased (0.48 ± 0.04μg / mg vs 1.37 ± 0.06μg / mg, P <0.05 respectively); the activation of hepatic fibroblasts Decreased - the expression of α-SMA decreased in liver tissue (both groups were 0.32 ± 0.05 vs.0.84 ± 0.14, P <0.05), and the expression of TGF-β1 decreased (the two groups were 0.69 ± 0.11 vs.1.31 ± 0.23, P (0.01) .Conclusion: Hepatocyte growth factor gene therapy can reduce the degree of hepatic fibrosis in the biliary ligation of hepatic fibrosis, and hepatocyte growth factor can be used in the treatment of hepatic fibrosis.