乌拉坦致C57BL/6J小鼠肺腺瘤动物模型方法研究

陈晨,盛云华,王宇,王巧旭,谷舒怡,胡玥,唐黎明

中国药学杂志 ›› 2018, Vol. 53 ›› Issue (9) : 701-706.

PDF(2869 KB)
PDF(2869 KB)
中国药学杂志 ›› 2018, Vol. 53 ›› Issue (9) : 701-706. DOI: 10.11669/cpj.2018.09.009
论著

乌拉坦致C57BL/6J小鼠肺腺瘤动物模型方法研究

  • 陈晨1,2,盛云华2,王宇2,王巧旭2,谷舒怡2,胡玥2,唐黎明2*
作者信息 +

Animal Model of Lung Adenoma in C57BL/6J Mice Induced by Urethane

  • CHEN Chen1,2, SHENG Yun-hua2, WANG Yu2, WANG Qiao-xu2, GU Shu-yi2, HU Yue2, TANG Li-ming2*
Author information +
文章历史 +

摘要

目的 采用3种不同的造模方法,比较并优化乌拉坦致 C57BL/6J小鼠肺腺瘤动物模型建立的方法。方法 取雌性 C57BL/6J 小鼠,分成4组,阴性对照组和模型Ⅰ组,模型Ⅱ组,模型Ⅲ组。模型Ⅰ组腹腔注射800 mg·kg-1乌拉坦,2次·周-1,连续5周;模型Ⅱ组腹腔注射1 000 mg·kg-1乌拉坦,2次·周-1,连续5周;模型Ⅲ组腹腔注射1 000 mg·kg-1乌拉坦,5 d·次-1,连续8次。阴性对照组给予等体积氯化钠注射液,给药方式与模型Ⅱ组相同。每周称量动物体重。所有组分别于第28周取主要脏器心、肝、脾、肺、肾、脑、胸腺,计算脏器指数,同时另取肺组织观察,计腺瘤数,量取肺腺瘤直径,并对肺、胸腺进行组织病理学检查。收集阴性对照组和模型组小鼠支气管肺泡灌洗液,对细胞进行分类计数分析。结果 与阴性对照组相比,3种造模方法均100 %诱导出肺腺瘤,模型Ⅰ组和模型Ⅲ组肿瘤数目均为6左右,模型Ⅱ组肿瘤数目大约为2。3组造模小鼠肺指数均增大,脑、脾、胸腺指数均减小,支气管肺泡灌洗液分析表明模型组淋巴细胞和多型核白细胞多于阴性对照组。结论 3种造模方法均100 %诱导出肺腺瘤,综合检测各指标,模型Ⅰ组和Ⅲ组相对于模型Ⅱ组诱导肺肿瘤的数目相对较多,模型较稳定均一。

Abstract

OBJECTIVE To compare and optimize the animal model of lung cancer on C57BL/6J mice by three different experimental methods.METHODS Female C57BL/6J mice were divided into four groups:control group, model group Ⅰ, Ⅱ and Ⅲ. The mice in model groupⅠreceived 800 mg·kg-1 urethane by intraperitoneal injection twice a week, followed by 5 weeks. The mice in model group Ⅱ were injected intraperitoneally with 1 000 mg·kg-1 urethane in the same way with model group Ⅰ. The mice in model group Ⅲ received urethane at the dose of 1 000 mg·kg-1 intraperitoneally, every 5 day continuing for 8 weeks. The control group was given equal volume of sodium chloride solutions in the same way as the model group Ⅱ. The main organs of all the groups were taken such as heart, liver, spleen, lung, kidney, brain and thymus at the 28th week, and their organs index was calculated. At the same time the lung tissues were examined to get the amount of adenomas and the diameters, and developed the lung and thymus histopathological examination. The bronchial alveolar lavage fluids were collected to classify the cells of the control and experimental groups.RESULTS Compared with the control group, all the three experimental groups could induce lung adenomas absolutely, the number of tumors in model groupⅠand Ⅲ was 6, while tumors in model Ⅱ group was about 2. In the three experimental groups the index of lung increased and the brain, spleen and thymus decreased compared with the control group. The bronchial alveolar lavage fluids analysis showed that the number of lymphocytes and polymorphonuclear leukocytes in the model group are more than that in control group.CONCLUSION All the three experimental groups could induce lung adenomas absolutely. Compared with model group Ⅱ, the model Ⅲ and Ⅰ are more stable and homogeneous with the similar results of experiment.

关键词

乌拉坦 / C57BL/6J小鼠 / 肺腺瘤 / 动物模型

Key words

urethane / C57BL/6J mice / lung adenoma / animal model

引用本文

导出引用
陈晨,盛云华,王宇,王巧旭,谷舒怡,胡玥,唐黎明. 乌拉坦致C57BL/6J小鼠肺腺瘤动物模型方法研究[J]. 中国药学杂志, 2018, 53(9): 701-706 https://doi.org/10.11669/cpj.2018.09.009
CHEN Chen, SHENG Yun-hua, WANG Yu, WANG Qiao-xu, GU Shu-yi, HU Yue, TANG Li-ming. Animal Model of Lung Adenoma in C57BL/6J Mice Induced by Urethane[J]. Chinese Pharmaceutical Journal, 2018, 53(9): 701-706 https://doi.org/10.11669/cpj.2018.09.009
中图分类号: R965   

参考文献

[1] CHEN W, ZHENG R, BAADE P D, et al. Cancer statistics in China, 2015 [J] . CA Cancer J Clin, 2016, 66(2):115.
[2] MEUWISSEN R, BERNS A. Mouse models for human lung cancer [J] . Genes Dev, 2005, 19(6):643-664.
[3] O′DONNELL E P, ZERBE L K, DWYER-NIELD L D, et al. Quantitative analysis of early chemically-induced pulmonary lesions in mice of varying susceptibilities to lung tumorigenesis [J] . Cancer Lett, 2006, 241(2):197-202.
[4] SCHMETIZ I, CHIONG K G, HOFFMANN D J. Formation and determination of ethyl carbamate in tobacco and tobacco smoke [J] . J Anal Toxicol, 1978, 2(6):265-268.
[5] OUGH C S. Ethylcarbamate in fermented beverages and foods. I. Naturally occurring ethylcarbamate [J] . J Agric Food Chem, 1976, 24(2):323-328.
[6] NETTLESHIP A, HENSHAW P, MEYER H. Induction of pulmonary tumors in mice with ethyl carbamate (urethane) [J] . Natl Cancer Inst, 1943,52(4):309-319.
[7] MILLER Y E, DWYERNIELD L D, KEITH R L, et al. Induction of a high incidence of lung tumors in C57BL/6 mice with multiple ethyl carbamate injections [J] . Cancer Lett, 2003, 198(2):139-144.
[8] MALKINSON A M. Genetic studies on lung tumor susceptibility and histogenesis in mice [J] . Environ Health Perspect, 1991, 93(2):149-159.
[9] KIM C F B, JACKSON E L, WOOLFENDEN A E, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer [J] . Cell, 2005, 121(6):823-835.
[10] SWEET-CORDERO A, MUKHERJEE S, SUBRAMANIAN A, et al. An oncogenic KRAS expression signature identified by cross-species gene-expression analysis [J] . Nature Genet, 2005, 37(1):48-55.
[11] STEARMAN R S, DWYER-NIELD L, ZERBE L, et al. Analysis of orthologous gene expression between human pulmonary adenocarcinoma and a carcinogeninduced murine model [J] . Am J Pathol, 2005, 176(6):1763-1765.
[12] GERADTS J, FONG K M, ZIMMERMAN P V, et al. Correlation of abnormal RB, p16(Ink4a), and p53 expression with 3p loss of heterozygosity, other genetic abnormalities, and clinical features in 103 primary non-small cell lung cancers [J] . Clin Cancer Res, 1999, 5(4):791-800.
[13] HERZOG C R, SOLOFF E V, MCDONIELS A L, et al. Homozygous codeletion and differential decreased expression of p15(INK4b) p16(INK4a)-alpha and p16(INK4a)-beta in mouse lung tumor cells [J] . Oncogene, 1996, 13(9):1885-1891.
[14] YOU M, CANDRIAN U, MARONPOT R R, et al. Activation of the Ki-ras protooncogene in spontaneously occurring and chemically induced lung tumors of the strain A mouse [J] . Proc Natl Acad Sci USA, 1989, 86(9):3070-3074.
[15] CLEMENTS N C, NELSON M A, WYMER J A, et al. Analysis of K-Ras gene-mutations in malignant and nonmalignant endobronchial tissue obtained by fiberoptic bronchoscopy [J] . Am J Respir Crit Care Med, 1995, 152(4):1374-1378.
[16] YOU M, WANG Y A, STONER G, et al. Parental bias of Ki-Ras oncogenes detected in lung-tumors from mouse hybrids [J] . Proc Natl Acad Sci USA, 1992, 89(13):5804-5808.
[17] MALKINSON A M, BEER D S. Pharmacologic and genetic studies on the modulatory effects of butylated hydroxytoluene on mouse lung adenoma formation [J] . Natl Cancer Inst, 1984, 73(4):925-933.
[18] KARASAKI H, OBATA M, OGAWA K, et al. Roles of the Pas1 and Par2 genes in determination of the unique, intermediate susceptibility of BALB/cByJ mice to urethane-induction of lung carcinogenesis:differential effects on tumor multiplicity, size and Kras2 mutations [J] . Oncogene, 1997, 15(15):1833-1840.
[19] WANG M, DEVEREUX T R, VIKIS H G, et al. Pol iota is a candidate for the mouse pulmonary adenoma resistance 2 locus, a major modifier of chemically induced lung neoplasia [J] . Cancer Res, 2004, 64(6):1924-1931.
[20] MALKINSON A M, BEER D S. Major effect on susceptibility to urethane-induced pulmonary adenoma by a single gene in BALB/cBy mice [J] . J Natl Cancer Inst, 1983, 70(5):931-936.
[21] XU C, ZHOU L, LU L, et al. Inflammation has a role in urethaneinduced lung cancer in C57BL/6J mice [J] . Mol Med Rep, 2016, 14(4):3323-3328.
[22] DAHL G A, MILLER J A, MILLER E C. Vinyl carbamate as a promutagen and a more carcinogenic analog of ethyl carbamate [J] . Cancer Res, 1978, 38(11):3793-3804.
[23] SUN T. The study of lung cancer model induce by urethane in mice [D] . Zhengzhou:Henan University, 2013.
PDF(2869 KB)

160

Accesses

0

Citation

Detail

段落导航
相关文章

/