小鼠原发性肝癌建模方法的优化  

Optimization of the establishment method of mouse model of hepatocellular carcinoma

作　　者：顾洪伟[1] 陈琦[1] 张炜[1] 李玉桑[1] 唐和斌[1] 

机构地区：[1]中南民族大学药学院药理学研究室,武汉430074

出　　处：《中国实验动物学报》2016年第1期20-24,共5页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金资助项目(No.81101538;No.81573887);中南民族大学中央高校科研基金(No.CZZ15007);湖北省自然科学基金项目(No.2015CFB496)

摘　　要：目的建立良好、快捷、稳定的小鼠原发性肝癌模型。方法将128只雄性KM小鼠随机均分为8组:正常组给予自由饮食;二乙基亚硝胺(DEN)水溶液组每天给予含DEN(16.5 mg/kg)的水溶液;高剂量DEN麻油组(7次/周、3次/周、1次/周),经口给予含DEN(16.5 mg/kg)的麻油溶液;而低剂量DEN麻油组、nano-DEN组、纳米载体组则分别每周经口给予含DEN(8.25 mg/kg)的麻油溶液和nano-DEN或同量的纳米载体。20周后,处死小鼠,取肝脏标本,固定后行HE染色。结果 (1)含DEN的各组小鼠均出现不同程度毛色枯燥、无光泽、行动迟缓、体重增长缓慢;(2)20周时,同DEN水溶液组,高剂量DEN麻油组小鼠均出现肿瘤,且其1次/周的小鼠死亡率较低;(3)Nano-DEN组小鼠无死亡,且其肝脏损伤的HE评分较低剂量DEN麻油组严重。结论 DEN溶于麻油的经口给药增加了小鼠服药的顺应性,长期低频率给药能大大降低造模过程中的死亡率。而DEN的纳米微乳制剂,能增强对肝脏的损伤程度。Objective To develop an efficient,fast and stable establishment method of mouse model of hepatocellular carcinoma. Methods 128 healthy Kunming male mice were equally divided into eight groups： normal group supplied with routine drinking water and food; diethylnitrosamine（ DEN）-water group received 16. 5 mg / kg DEN in drinking water every day; high-dose DEN-oil groups received orally 16. 5 mg / kg of DEN oil solution once,3 times and 7 times per week,respectively; low-dose DEN-oil group and nano-DEN group received orally 8. 25 mg / kg DEN in oil or in nano-vehicle every week,while nano-vehicle group received only an equal amount of nano-vehicle. After twenty weeks,all mice were sacrificed. The paraffin-embedded mouse liver specimens were examined by pathology using HE staining. Results（ 1）The mice treated with DEN solution showed dry and dull hair,slow movement and slow weight-gain to a varying degree.（ 2） At the twentieth week,both the DEN-water group and high-dose DEN-oil group showed tumors,and the mortality of high-dose DEN-oil group（ once per week） was low.（ 3） There was no death of mice in the nano-DEN group,and the pathological examination revealed more serious liver injury in the nano-DEN group than in the low-dose DEN-oil group（ once per week）. Conclusions Oral administration of DEN-oil improved the dietary compliance of mice,and the mortality can be reduced significantly by long-term low frequency DEN administration. Microemulsion preparation of DEN dissolved in oil may enhance the DEN-induced liver damage.

关 键 词：二乙基亚硝胺 原发性肝癌 纳米二乙基亚硝胺 

分 类 号：Q95-33[生物学—动物学]