二乙基亚硝胺诱导肝细胞癌癌前病变动物模型研究  

The animal model research of hepatic precancerous lesion induced by diethylnitrosamine

作　　者：刘蕊洁[1] 杨先照[1] 焦云涛 李莹[1] 张鹏[1] 叶永安[1] 

机构地区：[1]北京中医药大学东直门医院消化内科,北京100700

出　　处：《中西医结合肝病杂志》2015年第3期162-164,195,共3页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：2013年高等学校博士学科点专项科研基金(No.20130013110006)

摘　　要：目的:通过动态观察予二乙基亚硝胺(DEN)腹腔注射的大鼠在不同时间节点的肝脏大体形态及病理学特征,结合肝癌前特异性免疫组化指标,以明确DEN诱导肝细胞癌癌前病变形成的最佳时间点。方法:将56只大鼠随机分为正常组与模型组,模型组大鼠予50mg/kg DEN腹腔注射,每周1次,持续16周;正常组大鼠予生理盐水腹腔注射,每周1次,持续16周。实验分别于给药后第4、6、8、10、12、14及16周末取材,每次取材正常组2只、模型组4只,观察大鼠肝脏大体形态,并行HE、Masson染色及谷胱苷肽-S转移酶(GST-Pi)免疫组化检测。结果:随着DEN给药次数增加,病理观察显示,模型组大鼠在第4周表现为肝脏炎性反应,第6周可见纤维组织增生,第8周纤维间隔形成,第10周形成早期肝硬化,第12周形成肝硬化,第14周形成肝细胞癌前病变,第16周形成肝细胞癌。结论:予大鼠50mg/kg DEN腹腔注射,每周1次,可在第14周诱导肝细胞癌癌前病变模型形成,且安全性较好。Objective： Through dynamic observeation of the liver morphology,pathology and specific immunohistochemical index of the rats by the intraperitoneal injection of diethylnitrosamine（ DEN） to determine the best time of the hepatic precancerous lesion induced by DEN. Methods： Fifty-six rats were divided into the control group and the model group randomly. The model group was given DEN injection on the dose of 50 mg / kg once a week for 16 weeks,while the control group was given the same dose of saline. Two rats from the control group and four rats from the model group were selected randomly to sacrifice in the end of 4th,6th,8th,10 th,12th,14 th and 16 th week respectively to observe the morphology,pathology and specific immunohistochemical index. Results： With the usage of DEN in the model group,hepatitis was showed on 4th week,liver fibrosis was showed on 8th week,liver cirrhosis was showed on 12 th week,liver precancerous lesions was showed on 14 th week,and the hepatic carcinoma was showed on 16 th week finally. Conclusion： Injection by DEN on the dose of 50 mg /kg once a week for 14 weeks can induce the liver precancerous lesions with a relative safety.

关 键 词：癌前病变 肝细胞癌 二乙基亚硝胺 动物模型 

分 类 号：R735.7[医药卫生—肿瘤]