二乙基亚硝胺联合N-亚硝基吗啉诱导大鼠肝癌模型的实验病理研究

目的建立二乙基亚硝胺（diethylnitrosamine，DEN）联合Ⅳ-亚硝基吗啉（N-nitrosomorpholine，NMOR）诱导SD大鼠的肝癌模型并初步动态观察肝脏病理形态变化及肝癌肺转移。方法按100mS／kg体重腹腔注射一次DEN，第二天开始给予含100ppmNMOR饮水供鼠自由饮用的方法诱导SD大鼠肝癌模型，病理常规HE染色动态观察。结果病理学检查证实DEN＋NMOR成功诱导出具有转移能力的肝癌模型，20周时肝癌发生率为87．5％（21／24），肺转移发生率为47．6％（10／21）。病理过程大致经过肝细胞损伤期、肝细胞增生硬化期、肝细胞癌变和肺转移发生等时期。结论该肝癌模型可以作为研究人类肝癌发生、发展和转移的一种理想的动物模型。

STUDY ON MORPHOLOGIC FEATURES DURING HEPATOCELLULAR CARCINOMAS INDUCED BY DEN AND NMOR IN RATS

Objective To establish hepatocellular carcinomas model induced by DEN and NMOR and investigate the morphologic evolution during hepatocarcinogenesis in rats.Methods Sixty SD rats were given a single i.p.injection of DEN at a dose of 100 mg/kg body weight.and then were given 100 ppm NMOR in the drinking water for 20 weeks.Ten rats as Control group were only given a single i.p.injection of sodium chloride as the same volume of DEN.A series histopathology research was employed to examine the hepatic and pulmonary lesions in hepatocellular carcinoma model.Results By the end of 20 weeks,87.5% liver neoplasm and 47.6% lung metastases were identified by morphologic investigation.The procession of hepatocarcinogenesis in this model included three stages-hepatic toxic lesion,hepatic proliferation/cirrhosis,hepatic carcinogenesis and metastases.The rat model with HCCs induced with DEN and NMOR have similar forming procession and morphologic features to human hepatocellular carcinomas.Conclusions The model on hepatocarcinogenesis induced by DEN and NMOR in SD rat is an ideal experimental model for clinical medicine study.