Ⅳ型胶原酶门脉灌注治疗兔肝硬化有效性与安全性的观察

The effectiveness and safety of portal type Ⅳ collagenase administration on CCl_4 induced rabbit liver cirrhosis

目的应用四氯化碳(CCl4)诱导兔肝硬化模型,观察Ⅳ型胶原酶门脉灌注对肝硬化程度及全身重要器官组织病理学的影响。方法新西兰大白兔皮下注射50%CCl4橄榄油造模后,将已形成肝硬化并门静脉插管成功的30只兔随机分为2组,组1经门静脉给药通路注入0.1%Ⅳ型胶原酶1.5 mL,组2注入等量0.9%氯化钠,5次/周,共4周。4周后,将各组动物处死,留取各器官组织,观察其病理学变化。结果造模成功后可观察到典型肝硬化病理表现,门脉灌注0.1%Ⅳ型胶原酶肝硬化动物肝脏纤维化程度明显降低,门静脉、心脏、肺、肾脏、脑组织等部位组织病理学无异常表现。结论采用门脉灌注0.1%Ⅳ型胶原酶可显著降低肝纤维化程度,在此剂量下,具有一定的全身安全性。

Objective To observe the safety of portal collagenase administration, and to investigate the anti,fibrotic effects of Carbon tetrachloride. Methods New Zealand rabbits were injected 50% CCl4-olive oil subcutaneously with the dosage of 0.23 mL/kg twice a week. After the animal model was made, the portal delivery system （PDS） was intro- duced simultaneously. 30 rabbits with liver cirrhosis were randomly divided into 2 groups. The group 1 was injected 1. 5 mL of O. 1% type IV collagenase solution through PDS. The group 2 received the same volume of 0.9% sodium chlo- ride. The injection was conducted 5 times a week and continued for 4 weeks. All the animals were sacrificed after four- week＇ s injection, and the tissues of several important organs were removed for histological examination. Results The liver cirrhosis progressed gradually as continuous injection of the CCL4. Portal administration of collagenase significantly attenuated liver cirrhosis, but the histological examination was normal for portal vein, heart, lung, kidney and brain. Conclusion Portal administration of 0.1% type Ⅳ collagenase can significantly attenuate liver cirrhosis whereas it is safety in this dosage.