利用二乙基亚硝胺联合处理N-亚硝基吗啉和2/3肝部分切除方法改良的大鼠中晚期肝癌模型  

A modified rat model for advanced hepatocellular carcinoma treated by N-diethylnitrosamine combined with N-nitrosomorpholine and two-thirds partial hepatectomy

作　　者：张梅[1] 洪泽宣 邹昕羽 王剑[1] 王自力[1] 李晓清[2] 金美兰[1] ZHANG Mei;HONG Zexuan;ZOU Xinyu;WANG Jian;WANG Zili;LI Xiaoqing;JIN Meilan(College of Animal Science and Technology,Southwest University,Chongqing 400715,China;Chongqing Traditional Chinese Medicine Hospital,Chongqing 400021)

机构地区：[1]西南大学动物科技学院,重庆400715 [2]重庆市中医院肿瘤科,重庆400021

出　　处：《中国实验动物学报》2020年第5期638-644,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：中央高校基本业务费(XDJK2016B019)。

摘　　要：目的为建立适用于癌症研究的实验周期短、死亡率低、建模成本低和可转移的中晚期肝癌模型,对现有的方法进行了改良。方法实验开始时给所有的动物腹腔注射200 mg/kg DEN,同时第1组和第2组动物分别用含40、80 ppm NMOR染毒水饲养,对应时间分别为20周和10周。第3组动物采用灌胃方法给药0.8 mg/kg的NMOR,持续17周。为了增强细胞增殖活性,第1组和第3组动物在第2周结束时进行了2/3肝部分切除术。另外,NMOR的处理结束后第2组和第3组的动物需继续饲养7周。结果第1组在第20周时肝肿瘤发病率和生存率分别为10%和100%。第2组在第17周时肝肿瘤发病率为35%,生存率为76%。第3组在第24周时肝肿瘤发病率为100%,生存率为55%,肺转移率为55%。然而,第3组直到第20周为止,其生存率为100%。结论腹腔注射DEN,并进行2/3肝部分切除术及使用0.8 mg/kg的NMOR灌胃17周的方法,可在20周内建立生存率高、发病率高、后期可出现转移灶的中晚期肝肿瘤模型。该建模方法具有肝癌发病率高、模型生存率高和后期出现转移灶的优点,可为肝癌防治及机理研究提供理想的模型。Objective We aimed to improve an existing modeling method to establish an experimental model suitable for cancer research with short experimental period,low mortality,and modeling cost for metastasis.Methods Animals were injected intraperitoneally with 200 mg/kg N-diethylnitrosamine(DEN)at the beginning of the experiment.All animals in the first and second groups were given 40 or 80 ppm N-nitrosomorpholine(NMOR)via drinking water for 20 or 10 weeks.Animals in a third group were given 0.8 mg/kg NMOR via gavage for 17 weeks.Animals in the second and third groups were fed for 7 weeks following the NMOR treatment.All animals in the first and third groups were subjected to two-thirds partial hepatectomy(PH)to enhance cell proliferation activity at the end of the second week after DEN treatment.Results The first group had a liver tumor incidence of 10%,a survival rate of 100%,and a lung metastasis rate of 0%at 20 weeks.The second group had a liver tumor incidence of 35%,a survival rate of 76%,and lung metastasis rate of 0%at 17 weeks.The liver tumor incidence was 100%in the third group.The survival rate was 100%or 55%at 20 or 24 weeks.The lung metastasis rate was 55%.Conclusions Overall,these result suggest that modeling method such as intragastric administration of 0.8 mg/kg NMOR for 17 weeks after intraperitoneal injection of 200 mg/kg DEN and a twothirds PH can effectively establish an advanced liver tumor model with a high survival rate and morbidity in 20 weeks.In addition,metastases can appear at the later stages.This modeling method has several advantages,such as high incidence of hepatocellular carcinoma,high model survival rate,and late-stage metastasis.This could be an ideal model for research on the prevention and mechanism of hepatocellular carcinoma.

关 键 词：中晚期肝癌 动物模型 二乙基亚硝胺 N-亚硝基吗啉 

分 类 号：Q95-33[生物学—动物学]