DIPN诱发金仓鼠肝内胆管癌动物模型

目的 建立肝内胆管癌（ICC）动物模型，动态观察其发生发展的病理过程。方法 6周龄雄性金仓鼠，随机分为正常对照组、单纯结扎胆总管组织DIPN组，分别在实验的5、10及15周分批处死动物，观察其形态学变化。结果 诱癌早期出现卵圆细胞增生、管状增生及小胆管的囊性增生，中期主要病变为肝内胆管上皮乳头状增生、化生、不典型增生和胆管纤维化，晚期可见肝内胆管腺瘤和腺癌。其10周和15周肝内胆管癌的发生率分别是20％（1／10）和67．0％（10／15）。结论 该动物模型能够模拟人类肝内胆管癌发生发展的过程，方法简便，可重复性好，具有良好的应用前景。肝内胆管的各种增生性病变与ICC密切相关，尤其是不典型增生和胆管腺瘤，应视为ICC的高危性癌前病变。

Establishment of intrahepatic cholangiocarcinoma model induced by Diisopropanolnitrosoamine in Syrian hamsters

Objective To establish an intrahepatic cholangiocarcinoma (ICC) model in Syrian hamsters by injecting diisopropanolnitrosoamine (DIPN) and dynamically observe the pathological process of its genesis and development. Methods A total of 60 male Syrian golden hamsters at age of six weeks were randomly divided into 3 groups: control, simple common bile duct occlusion (S CBDO) and CBDO DIPN groups. CBDO DIPN group received weekly subcutaneous injection of DIPN at a dose of 500 mg/kg body weight after S CBDO. The animals were killed at the 5th, 10th and 15th week after the initatial administration of DIPN. The behaviors of the hamsters, gross and pathological changes of their livers were observed. Results Oval cell, tubular and cystic hyperplasia were seen at the early stage of induction, papillary, metaplastic and atypical hyperplasia and cholangiofibrosis at the middle stage, and adenoma, cholangiocellular carcinoma in intrahepatic bile duct at the end stage. The incidences of ICC were 20% (1/10) and 67% (10/15) respectively at the 10th and 15th week in the late stage of carcinoma induction. Conclusion The pathological changes of this simple and repeatable animal model may simulate the process of pathogenesis of ICC seen in human. Intrahepatic bile duct hyperplasia is closely correlated with ICC, especially atypical hyperplasia and adenoma are regarded as high risks for premalignant lesions of ICC.