四氯化碳复合、梯段用药法制备大鼠门脉高压模型的研究

Research of Portal Hypertension Model of Rats Built by Subcutaneous Injection of Carbon Tetrachloride

目的探讨构建一种稳定、可靠的门脉高压大鼠模型的制备方法,并研究该模型肝脏病理结构以及血流动力学的改变。方法雄性SD大鼠95只,体重150～170g,按编号法随机分为模型组和对照组。模型组:按0.4mL/100g剂量予以背部皮下注射50%CCl4橄榄油溶液,每周2次,持续4周。第5周开始改为以0.5mL/100g标准注射,每周2次,持续4周。对照组:仅注射橄榄油,频度及剂量同模型组。结果对照组10只大鼠全部存活。模型组85只大鼠,死亡24只,死亡率28%。存活61只大鼠,肝脏均可观察到纤维组织不同程度地增生,肝小叶结构破坏,假小叶形成,模型成功率100%。模型组门静脉压力和门静脉内径比对照组明显增加(P<0.05);血清TB、ALT及AST较正常对照组均明显升高(P<0.05),而ALB则明显降低(P<0.05)。结论该方法所构建的动物模型其组织学改变与人类肝硬变相似,门静脉压力显著增高,是研究门脉高压症的理想模型。

Objective To establish a steady,credible rat model of portal hypertension.Study its pathological changes of liver and the change of hemodynamics.Methods 95 male SD rats,weight 150～170g,were randomly devided into two groups.The experiment group（n=85）was injected 50% CCl4 subcutaneous at a dose of 0.4mL/100g on the back of rats twice a week,which lasted for 4 weeks.From the fifth week,the rats were injected CCl4 by dosage of 0.5mL/100g,twice a week and lasted for 4 weeks.Equal volume of olive oil was given to the rats in contral group.Results The control group rats all sruvived.The mortality of the experiment group was 28%,there were 24 died among the 85 rats.We could see fibrous tissue hyperplasia of liver,disorganization of hepatic lobule and pseudolobule.The portal venous pressure and internal diameter of portal vein raised obviously between the experiment group and the control group（P〈0.05）.Compared with that in control group,the liver function profile was significantly increasedin experiment group（P〈0.05）.Conclusion The procedure of constructing an animal model is fairly stable and reliable,the histological changes similar to human cirrhosis,portal vein pressure increased significantly,the model is useful for research in liver cirrhosis with portal hypertension.