摘要
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 exam the therapeutic efficacy of hepatocyte growth factor （HGF） gene therapy in a bile duct ligation liver fibrosis model. Methods： Male CD-1 mice were randomized into 3 groups, the normal group merely underwent surgery without bile duct ligation, the other 2 groups underwent bile duct ligation, received biweekly injection of pCMV-HGF （1μg/g）, or pcDNA3 respectively. The severity of liver fibrosis was evaluated at 3 months after bile duct ligation. Results： HGF gene therapy markedly attenuated collagen deposition, as showed by Masson-Trichrome staining and immunofluorescence staining of collagen Ⅰ,Ⅲ in the peri-biliary regiorn. Compared with pcDNA3 treated group, HGF gene therapy could significantly suppress hepatic myofibroblast activation, which was demonstrated by reduction of α-SMA expression （0. 32± 0. 05 vs. 0.84±0. 14, P〈0.05）, decrease the hydroxyproline content （0. 48±0. 04μg/mg vs. 1.37±0. 06μg/mg, P〈0. 05）, suppress expression of transforming growth factor-β1 （0. 69±0. 11 vs. 1.31±0. 23, P〈0. 01）. Conclusion： It suggested that HGF gene therapy could attenuate liver fibrosis induced by bile duct ligation and HGF may provide an effective therapeutic strategy for the treatment of chronic liver fibrosis.
出处
《中国临床医学》
北大核心
2005年第4期606-608,共3页
Chinese Journal of Clinical Medicine
关键词
肝细胞生长因子
基因治疗
肝纤维化
胆管结扎
Hepatocyte growth factor （HGF）
Gene therapy
Liver fibrosis
Bile duct ligation
