肝硬化大鼠模型的建立及其稳定性

Establishment and stability of hepatic cirrhosis rat models

目的:探讨肝硬化动物模型(CM)的建立及其稳定性。方法:80只Wistar大鼠,雌雄各半。分别采用复合因素法、四氯化碳(CCl4)加乙醇法及玉米面、胆固醇加乙醇法建立大鼠肝硬化的模型(假小叶形成为判定CM成功的唯一标准)。复合因素法:40只大鼠,饲料为80%的玉米面、20%的动物油、0.5%胆固醇,饮料仅为15%的酒精,首次皮下注射40%CCl4-橄榄油溶液5 mL.kg-1(以下浓度相同),以后每3 d皮下注射CCl43 mL.kg-1。第6周末随机处死6只大鼠做肝脏病理,均符合肝硬化诊断标准。将余下存活的26只(逃逸2只、死亡6只)随机分为两组,每组13只均正常饲养,其中一组每7 d皮下注射3 mL.kg-1CCl4,观察第7、8周末的病理变化。CCl4加乙醇法:20只大鼠,以正常饲料喂养,余条件同复合因素法前6周。玉米面、胆固醇加乙醇法:20只大鼠,不用CCl4,余条件同复合因素法前6周。结果:复合因素法6周末处死6只大鼠均形成CM,成模后正常饲养,2周后假小叶均消失,而继续应用CCl42周后,大鼠假小叶基本存在。其余2种方法大鼠均未见典型肝硬化改变。结论:采用复合因素法建立的CM形成率高,成模后CCl4的应用能够保持CM的相对稳定。

Objective To study the establishment and stability of hepatic cirrhosis animal model （CM）. Methods The methods of compound factor, carbon tetrachloride （CCl4） plus alcohol, corn flour and cholesterol plus alcohol were used to construct the hepatic cirrhosis rat models. 80 Wistar rats were selected, male and female were 40, respectively. There were 40 Wistar rats treated with compound factor method. The fodder feed was 80% corn flour, 20% animal oil, and 0.5% cholesterol, the only beverage was 5% alcohol . At the first time, the Wistar rats were administered with 40% CCl4-olive oil mixture by subcutaneous injection （5 mL·kg^-1 ）. Then they were hypodermically injected with 40 % CCl4-olive oil mixture （3 mL· kg^-1） every 3 days for six weeks. At the end of the 6th week, six Wistar rats were executed randomly and made into hepatic smears which were accorded with hepatic cirrhosis （The forming of pseudolobuli was the only standard to decide the successful establishment of CM）. The rest rats were randomly divided into two groups. There were 13 Wistar rats treated with normal fodder feeding in each group. Meanwhile the rats in one group were hypodermically injected with 40% CCl4-olive oil mixture （3 mL· kg^-1 ） every 7 days. Then the pathological changes at the end of 7th and 8th week were observed. TwentyWistar rats treated with CCl4 plus alcohol were fed with normal fodder food. Remaining conditions were as same as those were used in the first 6 weeks of compound faetor method. Twenty Wistar rats treated with eorn flour and cholesterol plus alcohol weren＇t hypodermically injeeted with CCl4 and remaining conditions were same with those were used in the first 6 weeks of eompound faetor method. Results The rat models with hepatie eirrhosis treated with compound faetor were established eompletely at the end of 6th week. Then the rats were fed with normal fodder food. Pseudolobuli were all disappeared after two weeks. And the rats were hypodermieally injeeted with eel4 for 2 weeks after establishment of CM, pseudolobuli were mainly existed. Typieal CM were not eonstructed with other two methods. Oonelusion The forming rate of hepatie eirrhosis model eonstrueted with eompound factor is high. After establishment of the model, CCl4 can keep the relative stability of the models.