肝内胆管癌动物模型的建立

Establishment of intrahepatic cholangiocarcinoma induced by aminopyrine and sodium nitrite in syrian hamsters

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 以浓度为 80 0mg/L的氨基比林和亚硝酸钠溶液作为叙利亚地鼠的饮用水 ,每周饮用 6d ,连续饮用 2 4周 ,定期分批处死动物 ,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。晚期肝内胆管癌的发生率达 5 0 .0 % (10 /2 0 )。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 ,经济 ,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。

Objective To establish intrahepatic cholangiocarcinoma (ICC) in syrian hamsters by combination of aminopyrine and sodium nitrite and dynamically observe the pathologic process of its development.Methods Syrian hamsters received 800 mg/L aminopyrine and 800 mg/L sodium nitrite in their drinking water in 6 consecutive days in a week, with tap water on the remaining day for 24 weeks. At 4, 8, 12, 16, 20 and 24 weeks of treatment groups, 5 to 10 animals were killed and the pathological changes were observed. Results Hyperplasia of oval cells and tubular hyperplasias, cystic hyperplasias, papillary hyperplasias, metaplasias, atypical hyperplasias, cholangiofibrosis, adenomas, cholangiocellular carcinomas of intrahepatic bile duct were successfully induced. The incidence of ICC was 50.0% (10/20) in the late stage of carcinoma induction.Conclusion The pathological changes of the animal model were similar to those seen in human. This model was simple, economical and repeatable. There was a close relation betweeen intrahepatic bile duct hyperplasia and ICC. Intrahepatic bile duct atypical hyperolasia and adenoma are high risks for premalignant lesions of ICC.