目的 CCl4皮下注射建立兔肝硬化动物模型,观察Ⅳ型胶原酶门静脉灌注对肝硬化及肝组织中α-平滑肌动蛋白(α-SMA)表达的影响。方法取雄性新西兰大白兔,采用臀部皮下注射50%CCl4橄榄油0.23ml/kg,每周2次,共12周制作肝硬化动物模型,注射等量橄榄油作为对照。12周后各组动物均建立门静脉给药通路,将已形成肝硬化并门静脉插管成功的33只兔随机分为两组(组1,组2),组1为16只、组2为17只。组1经门静脉给药通路注入0.1%Ⅳ型胶原酶1.5ml,组2注入等量0.9%氯化钠,5次/周,共4周。将造模对照组中门静脉插管成功的30只兔同样随机分为两组(组3,组4),每组15只,处理方法同前。4周后,将各组动物处死后留取肝脏组织,观察其病理学及羟脯氨酸含量变化,标本固定后,行α-SMA免疫组织化学染色,行积分光密度、面密度分析。结果肝硬化动物肝脏α-SMA表达显著增强;门静脉灌注0.1%Ⅳ型胶原酶肝硬化动物肝脏纤维化程度明显降低,羟脯氨酸含量显著降低,但α-SMA表达强度显著增高。结论采用门静脉灌注0.1%Ⅳ型胶原酶可显著降低肝纤维化程度,但α-SMA表达增高,可能与肝脏星状细胞激活有关。 Objective To establish an animal model of hepatic cirrhosis by subcutaneous injection with CCl4 and observe the effect of type Ⅳ collagenase on the expression of α-smooth muscle actin (α-SMA) in liver cirrhosis and liver tissue. Methods Male New Zealand white rabbits were injected subcutaneously with 0.23 ml / kg 50% CCl4 olive oil in the buttocks twice a week for 12 weeks to make cirrhosis animal model, and the same amount of olive oil was injected as the control. Twelve weeks later, all the animals in each group were given the portal vein access route. Thirty-three rabbits who had formed cirrhosis and portal vein catheterization were randomly divided into two groups (group 1 and group 2). Group 1 was 16 and group 2 was 17 only. In group 1, 1.5ml of type Ⅳ collagenase (1.5ml) was infused through the portal vein, and group 2 was injected with 0.9% sodium chloride equivalent to 5 times a week for 4 weeks. Thirty rabbits with successful portal vein catheterization in the model control group were also randomly divided into two groups (Group 3, Group 4) with 15 rats in each group. The treatment method was the same as before. Four weeks later, the liver tissue was collected and the pathological changes and hydroxyproline content were observed after the animals were sacrificed. Α-SMA immunohistochemical staining was performed after the specimens were fixed, and the integral optical density and surface density were analyzed. Results The hepatic α-SMA expression was significantly increased in cirrhotic animals. Liver fibrosis in liver cirrhosis animals with portal vein perfusion of 0.1% collagenase was significantly reduced, while the content of hydroxyproline was significantly decreased. However, the expression of α-SMA was significantly increased. Conclusion Intravenous infusion of 0.1% collagenase Ⅳ can significantly reduce the degree of hepatic fibrosis, but α-SMA expression may be related to the activation of hepatic stellate cells.