目的:观察不同剂量二乙基亚硝胺(DEN)诱发大鼠肝癌效果,确定合适诱癌剂量.方法:将96只100～150g Wistar SPF级雄性大鼠随机分为DEN自由饮水40ppm(A组)、64ppm(B组)、80ppm(C组)及自来水自由饮用组(D组),每组24只,普通饲料喂养,于第16周各组处死12只,取肝组织,观察肝脏形态以及成癌情况,送检病理.各组剩余12只用于观察生存期.结果:第16周诱癌各组未见1例大鼠死亡.病理学检查证实A、D组成癌率为0,B、C组诱癌率分别为83.33%、91.66%,两组成癌率比较无统计学差异;C组可见一巨块型肝癌,A组均表现为肝细胞炎症、水肿、点状坏死、结缔组织轻度增生,小灶脂肪变性.B组肝脏表面弥漫性出现局灶区域肝细胞非典型性增生,癌周结缔组织增生,未发现典型肝硬变表现,C组癌周组织肝细胞弥漫性水肿变形、点状坏死、汇管区炎细胞侵润、结缔组织增生,肝小叶结构大部分破坏.DEN诱发的肝癌为肝细胞癌.结论:以64ppm、80ppm DEN均可作诱癌剂量,64ppm诱癌在生存期方面优于80ppm,64ppm浓度诱癌是一种较理想的用于药物疗效评价的大鼠肝癌模型.%Objective:To observe the effects of different concentration of diethylnitrosamine (DEN) in duced hepatocellular carcinoma model in rats, determine appropriate DEN dose to induced cancer, and ensure the post-experimental research. Methods: SPF male Wistar rats 96, weighing 150to 200g, were randomly divided into 4 groups(A, B,C,D). Groups A, B, C drinking water contained 40, 64, 80 ppm DEN for 16 weeks. The control drank the routine table- water. After 16 weeks, every group was sacrificed 12 rats, liver tissue, as well as observa-tion of liver cancer cases morphological examination and pathology. The remaining 12 rats in each group were to be observed the survival periods. Results: After 16w, there were no rats died of cancer. Pathological examination con-firmed that at 16th week, group A and D caught cancer was 0, group B induced cancer rate was of 83. 33%, C groups cancer rate was of 91. 16％, no significant difference in cancer rate between two groups. Group C showeds a bulky liver cancer, group A showed inflammation, edema, punctate necrosis , mild connective tissue proliferation, fatty degeneration. The liver surface of the group B showed diffuse focal areas of a typical hyperplasia of liver cells, peritu moral connective tissue proliferation, did not find the performance of typical cirrhosis,the non-cancerous liver tissue of the group C showed deformation diffused edema, dotty-necrosis,per portal, inflammatory infiltration, con-nective tissue hyperplasia, lobular structure of most of the damage. DEN induced hepatocellu-lar carcinoma was HCC,rat hepatocellular carcinogenesis process roughly after liver cell injury, liver cell hyperplasia, hardening period and hepatocellular carcinogenesis period of three phrases. Similar to human liver cancer with the process and patho-logical changes characteristic lesions. Conclusion: Both of the concentration of 64ppm,80ppm DEN can be used as in-duced cancer dose,64ppm induced in cancer survival maybe more effectiveness than 80ppm. 64ppm concentration in-duced cancer is an ideal for the evaluation of drug efficacy in rat liver cancer model.
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