四氯化碳皮下注射诱导兔肝纤维化模型

Liver Fibrosis Model in Rabbit Induced by Subcutaneous Injection of Carbon Tetrachloride

目的采用四氯化碳(CCl4)皮下注射诱导兔肝纤维化模型。方法 36只新西兰白兔随机分组:实验组30只、对照组6只。实验组开始2周颈背部皮下注射50%CCl4橄榄油0.3 m L/kg,随后10周注射0.2 m L/kg,每周各2次;对照组注射等量橄榄油。实验组及对照组分别于第4、8、12周末,检测兔肝脏功能生化指标的变化,以及肝脏大体和组织病理学变化,观察肝纤维化的发展程度。结果造模期间实验组家兔死亡6只,动物死亡率20%,对照组家兔无死亡。实验组兔肝脏纤维化程度随造模时间延长而逐渐加重,血清谷丙转氨酶、谷草转氨酶和γ-谷氨酰转移酶均明显升高,肝组织出现假小叶结构,造模成功率为80%。对照组肝脏功能以及组织学结构正常。结论长期持续给予四氯化碳可导致家兔的肝纤维化形成,成模率较高,并有较明显的阶段性变化,可进一步用于相关实验研究。

Objective To use subcutaneous injection of carbon tetrachloride （CCl4） to induce hepatic fibrosis model in rabbit. Methods 36 New Zealand white rabbits were divided into the experimental group （n = 30） and the control group （n = 6） randomly. The rabbits of experimental group were treated by subcutaneous injection of 50% CCl4 0.3 mL/kg in olive oil twice a week for the initial two weeks, then were treated by subcutaneous injection of 50% CCl4 0.2 mL/kg in olive oil twice a week for the next 10 weeks. The rabbits of control group were treated by same amount of olive oil. Rabbits＇ liver function, biochemical indicators, liver gross, histopathological changes and hepatic fibrosis degree were detected in experimental group and control group at 4m, 8m, and 12m week respectively. Results 6 rabbits were dead in experimental group during the period of molding, and animal mortality rate was 20%. No dead case was found in control group. In experimental group, rabbits＇ liver fibrosis degree increased gradually with molding time extension. Serum alanine aminotransferase, aspertate aminotransferase, and gamma glutamyl transpeptidase increased significantly, while their liver tissue appeared false flocculus structure, and molding success rate was 80%. The liver fimction and histological structure of control group were normal. Conclusions Injecting CCL for a long time may lead to the formation of liver fibrosis in rabbits, with significant difference in different time and high success rate. The model can be used further in related experiments.