摘要
目的 使用三种造模方法以建立小鼠的原发性肝癌模型,并比较各自的优缺点。方法 将80只14~16日龄的C57BL/6雄性小鼠随机分为4组(低剂量DEN组、高剂量DEN组、DEN+CCl4组、对照组):低剂量DEN组小鼠腹腔注射浓度为25 mg/kg的二乙基亚硝胺(diethylnitrosamine,DEN)染毒;高剂量DEN组小鼠腹腔注射浓度为40 mg/kg的DEN染毒;DEN+CCl4组小鼠腹腔注射2 mg/kg的DEN染毒,两周后按20%浓度的四氯化碳(carbon tetrachloride,CCl4)按5 m L/kg剂量腹腔注射小鼠,每周给药2次共16周;对照组不予任何处理。统计各组小鼠的生存情况,各组小鼠在造模的第24周集中麻醉断颈处死后剖取肝,比较各组间肝的外观、肿瘤的数目及肿瘤的发生率,并检测血清中谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、高尔基体跨膜糖蛋白73(Golgi protein 73,GP73)以及甲胎蛋白(alpha fetoprotein,AFP)的水平。结果 与对照组相比,三个实验组的ALT(P<0. 001)、AST(P<0. 001)、GP73(P<0. 001)、AFP (P<0. 01)、肿瘤发生率(P<0. 001)和肿瘤数目显著增加(P<0. 001)。截止造模后的24周,低剂量DEN组小鼠死亡率为15%,肝癌发生率为35%;高剂量DEN组小鼠死亡率为30%,肝癌发生率为86%;DEN+CCl4组小鼠死亡率为20%,肝癌发生率为56%;对照组小鼠全部存活且肝未发现异常。结论 各实验组的造模方法均可以成功进行小鼠肝癌造模,但高剂量DEN组表现出了明显的优势,它可以在短时间内成功的建立起高发生率且稳定的小鼠原发性肝癌模型,为小鼠肝癌造模提供了新的途径。
Objective To establish a model of primary liver cancer in mice using three method,and to compare their advantages and disadvantages.Methods Eighty male C57BL/6 mice aged 14–16 days were randomly divided into four groups:control,low-dose diethylnitrosamine(DEN),high-dose DEN,and DEN+carbon tetrachloride(CCl4).Mice in the DEN+CCl4 group were intraperitoneally injected with 2 mg/kg DEN,and then two weeks later CCl4(5 mL/kg,20%)was intraperitoneally injected twice a week for 16 weeks.The control group was not administered any treatment.Mice in the low-dose DEN group were injected intraperitoneally with 25 mg/kg DEN,while mice in the high-dose DEN group were intraperitoneally injected with 40 mg/kg DEN.Survival curves were generated for mice in each group.Twenty-four weeks after establishing the model,mice in each group were anesthetized and sacrificed,and the liver was dissected.The appearance of liver,incidence of tumors,number of tumors,and serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),Golgi protein 73(GP73),alpha fetoprotein(AFP)were measured.Results Compared with the control group,ALT(P<0.001),AST(P<0.001),GP73(P<0.001),AFP(P<0.01),tumor incidence(P<0.001),and tumor number in the three groups were significantly increased(P<0.001).By 24 weeks after modeling,three mice in the low-dose DEN group had died,while six out of the 17 surviving mice developed liver cancer,Results ing in an incidence of 35%.In the high-dose DEN group,six mice died and 12 out of the 14 surviving mice developed liver cancer,Results ing in an incidence rate of 86%.In the DEN+CCl4 group,four mice died and 9 out of the 16 surviving mice developed liver cancer,Results ing in an incidence rate of 56%.All mice in the control group survived and no liver abnormalities were observed.Conclusions The liver cancer mouse model was successfully established in all experimental groups,but the high-dose DEN group exhibited obvious advantages with regard to successful establishment of a primary liver cancer model with high inc
作者
孙振宇
武鸿彪
刘宁
徐胤淇
周健
陈雪健
王伟
徐力善
袁旦平
SUN Zhenyu;WU Hongbiao;LIU Ning;XU Yinqi;ZHOU Jian;CHEN Xuejian;WANG Wei;XU Lishan;YUAN Danping(Ningbo First Hospital,Ningbo 315000,China;The Fourth Hospital Affiliated to Harbin Medical University,Harbin 150001;Institute of Bioengineering,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850)
出处
《中国比较医学杂志》
CAS
北大核心
2019年第11期22-27,49,共6页
Chinese Journal of Comparative Medicine
基金
国家自然科学基金资助项目(31670761)
关键词
原发性肝癌
小鼠模型
二乙基亚硝胺
四氯化碳
化学诱导法
primary liver cancer
mouse model
diethylnitrosamine
carbon tetrachloride
chemical induction
