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机构地区:[1]上海交通大学医学院附属仁济医院普外科,上海200127
出 处:《肝胆胰外科杂志》2014年第1期48-50,54,共4页Journal of Hepatopancreatobiliary Surgery
基 金:上海市教委资助项目(13yz040)
摘 要:目的 探索一种稳定可靠的建立小鼠肝纤维化模型的方法.方法 46只6~8周龄雄性C57BL/6小鼠随机分为模型组和对照组,模型组分别给予浓度为15%、30%和45%的四氯化碳(CCl4)腹腔注射,每周2次,共12周;对照组给予同等剂量的橄榄油.最后一次注射结束3d后处死小鼠,评估肝纤维化程度;血清生化检测谷丙转氨酶(ALT)、谷草转氨酶(AST)和白蛋白(Alb); Western blotting检测肝内IL-6、TGF-β1蛋白水平.结果 模型组小鼠肝脏逐渐出现纤维化,其中45%组已有肝硬化表现.15%、30%和45%组的小鼠死亡率和建模成功率分别为8.3%、16.7%、41.7%和27.3%、80.0%、57.1%.与对照组此,随注射浓度增高,模型组血清ALT、AST含量逐渐升高(P<0.01),Alb逐渐降低(P< 0.01);IL-6和TGF-β1含量也逐渐升高(P<0.05).结论 注射30% CCl4 12周能够诱导明显的肝纤维化形成,建模成功率较高,且死亡率较低,是一种较理想的制作肝纤维化模型的方法,为研究肝纤维化的发病机制奠定了基础.Objective To explore a reliable method of establishment of hepatic fibrosis model in mice Methods Forty-six male C57BL/6 mice were randomly devided into control group and model group, and mice in model group were given 15%, 30% or 45% carbon tetrachloride (CCl4) via intraperitoneal injection for 12 weeks, twice per week; mice in control group were given the same dose of olive oil. Mice were sacrificed 3 d after the injection was finished. The degree of hepatic fibrosis was evaluated. The changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin (Alb) were detected with serum biochemistry; protein levels of IL-6 and TGF- β1 in liver tissue were determined by Western blotting. Results There was progressive hepatic fibrosis in model group and liver cirrhosis was appeared in 45% group. In 15%, 30% and 45% group, the mortality and success rate of mice were 8.3%, 16.7%, 41.7% and 27.3%, 80.0%, 57.l%. With the increase of injection concentration, the content of serum ALT and AST were increased gradually (P〈0.01), but the content of Alb was decreased gradually (P〈0.01); the expression of IL-6 and TGF-β1 in 45% group were also increased than that of the controls (P〈0.05). Conclusion Obvious hepatic fibrosis can be induced by the injection of 30% CCl4 for 12 weeks, and there are higher success rate and lower mortality. It is an ideal method for liver fibrosis model development, which lay a solid foundation for studying the pathogenesis of liver fibrosis.
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