二乙基亚硝胺诱发大鼠肝纤维化-肝癌动物模型的建立

目的 建立大鼠肝纤维化-肝癌模型并动态观察大鼠肝纤维化-肝癌发生过程中的病理形态特点.方法 用0.01％二乙基亚硝胺（DEN）溶液间断喂养SD大鼠诱发肝癌,对大鼠肝脏在不同诱癌阶段的病理变化进行动态观察.结果 用药第4周后,肝细胞点状坏死及炎性细胞浸润;8周时,肝细胞严重脂肪变性、灶性坏死,门管区出现纤维组织增生;9-12周时,增生的胶原束包绕并分割肝小叶,正常的肝小叶结构被破坏,假小叶形成;15周后存活大鼠均形成肝癌,肝癌细胞排列成条索状或团块状,诱癌组为100％成癌（8/8）.结论 成功建立从肝纤维化发展成肝癌的动物模型,设立间歇期提高了大鼠癌变末期的成活率,该模型是动态研究肝癌发生发展进程的理想动物模型.

DEN-induced Hepatic Fibrosis-carcinoma in Rats

Objective To establish diethylinitrosamine（DEN）-induced hepatic fibrosis-carcinoma model in rat and observe pathological features during the process of hepatic carcinoma.Method Sprague-Dawley rats were randomly divided into DEN group and normal control group.The rats of DEN group were administrated 0.01％ DEN solution in water for 18 weeks,and the control group received vehicle.The animals were sacrificed at the end of 4th,8th,10th,12th,15th week,respectively.Liver tissue sections were stained with hematoxylin-eosin （HE）.Result In DEN group,on 4th week,spotty necrosis of hepatocytes and inflammatory cell infiltration occurred in hepatic lobule.On 8th week,severe focal necrosis and hepatic steatosis of hepatocytes were observed accompanied with fiberous tissue proliferation in portal area.Hepatic lobules were encysted and separated by hyperplastic collagen bundles,and the normal structure of lobules was destroyed,and pseudo lobules formed on 9-12th week.After 16th week,the remaining surviving rats all developed hepatocellular carcinoma.The structure of liver tissue was normal in control group.Conclusion The intermission of DEN administer for hepatocellular carcinoma induction can elevate survival rate of rats in the end of carcinoma-inducing experiment.It is an ideal animal model for dynamically observing the pathologic process of hepatocellular carcinoma development.