| p53+/-基因敲除小鼠尿烷致癌性初步验证试验 |
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| 引用本文： | 李芊芊,霍桂桃,吕建军,杨艳伟,刘甦苏,范志云,祝清芬,国明,王三龙,王雪,范昌发. p53+/-基因敲除小鼠尿烷致癌性初步验证试验[J]. 中国药事, 2018, 32(7): 932-939 |
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| 作者姓名： | 李芊芊 霍桂桃 吕建军 杨艳伟 刘甦苏 范志云 祝清芬 国明 王三龙 王雪 范昌发 |
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| 作者单位： | 中国食品药品检定研究院, 药物非临床安全评价研究北京市重点实验室, 北京 100176,中国食品药品检定研究院, 药物非临床安全评价研究北京市重点实验室, 北京 100176,中国食品药品检定研究院, 药物非临床安全评价研究北京市重点实验室, 北京 100176,中国食品药品检定研究院, 药物非临床安全评价研究北京市重点实验室, 北京 100176,中国食品药品检定研究院, 药物非临床安全评价研究北京市重点实验室, 北京 100176,山东省食品药品检定研究院, 济南 250101,山东省食品药品检定研究院, 济南 250101,山东省食品药品检定研究院, 济南 250101,中国食品药品检定研究院, 药物非临床安全评价研究北京市重点实验室, 北京 100176,中国食品药品检定研究院, 药物非临床安全评价研究北京市重点实验室, 北京 100176,中国食品药品检定研究院, 药物非临床安全评价研究北京市重点实验室, 北京 100176 |
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| 基金项目： | 科技部“十二五”重大新药创制专项课题（编号2012ZX09302001） |
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| 摘 要： | 目的：观察自主建立的p53+/-敲除小鼠（命名为B6-Trp53tm1/NIFDC）模型，在给予尿烷后的体重、脏器重量、血液学及血生化指标变化，为该模型将来用于临床前药物短期致癌性试验的替代试验提供背景数据。方法：共设计3个组：阴性对照组（野生型小鼠，给予生理盐水）、尿烷组1（B6-Trp53tm1/NIFDC小鼠，给予1000 mg·kg-1尿烷）、尿烷组2（野生型小鼠，给予1000 mg·kg-1尿烷），各组动物数量均为20只，雌雄各半。试验期间及试验结束测定各组动物的体重、脏器重量和相对脏器重量、血液学及血生化指标，并进行统计分析。结果与结论：与阴性对照组相比，尿烷给药第2、3、11及21周尿烷组1和尿烷组2动物的体重显著下降；尿烷组1动物肺脏和脾脏绝对重量显著升高；尿烷组1和尿烷组2动物肺脏相对重量显著升高；尿烷组1动物NEU、RDW%、CHDW%以及尿烷组2动物LYM%、BASO%显著升高；尿烷组1及尿烷组2动物的血生化指标无明显改变。
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| 关 键 词： | p53+/-敲除小鼠 尿烷 脏器重量 血液学指标 血生化指标 |
| 收稿时间： | 2018-03-25 |
Preliminary Carcinogenicity Validation Study of p53+/- Knockout Mice Using Urethane |
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| Li Qianqian,Huo Guitao,Lv Jianjun,Yang Yanwei,Liu Susu,Fan Zhiyun,Zhu Qingfen,Guo Ming,Wang Sanlong,Wang Xue and Fan Changfa. Preliminary Carcinogenicity Validation Study of p53+/- Knockout Mice Using Urethane[J]. Chinese Pharmaceutical Affairs, 2018, 32(7): 932-939 |
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| Authors: | Li Qianqian Huo Guitao Lv Jianjun Yang Yanwei Liu Susu Fan Zhiyun Zhu Qingfen Guo Ming Wang Sanlong Wang Xue Fan Changfa |
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| Affiliation: | National Institutes for Food and Drug Control, Beijing Key Laboratory for Safety Evaluation of Drugs, Beijing 100176, China,National Institutes for Food and Drug Control, Beijing Key Laboratory for Safety Evaluation of Drugs, Beijing 100176, China,National Institutes for Food and Drug Control, Beijing Key Laboratory for Safety Evaluation of Drugs, Beijing 100176, China,National Institutes for Food and Drug Control, Beijing Key Laboratory for Safety Evaluation of Drugs, Beijing 100176, China,National Institutes for Food and Drug Control, Beijing Key Laboratory for Safety Evaluation of Drugs, Beijing 100176, China,Shandong Institute for Food and Drug Control, Jinan 250101, China,Shandong Institute for Food and Drug Control, Jinan 250101, China,Shandong Institute for Food and Drug Control, Jinan 250101, China,National Institutes for Food and Drug Control, Beijing Key Laboratory for Safety Evaluation of Drugs, Beijing 100176, China,National Institutes for Food and Drug Control, Beijing Key Laboratory for Safety Evaluation of Drugs, Beijing 100176, China and National Institutes for Food and Drug Control, Beijing Key Laboratory for Safety Evaluation of Drugs, Beijing 100176, China |
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| Abstract: | Objective:To observe the changes of body weight, organ weight, hematological and blood biochemical parameters of p53+/- knockout mice named as B6-Trp53tm1/NIFDC, after administration of Urethane and to provide background data for using the p53+/- knockout model as an alternative model for short-term carcinogenicity study in the field of preclinical safety evaluation of drugs. Methods:A total of three different groups were used, including negative control group (wild type C57BL/6 mice administrated with saline solution), Urethane group 1 (B6-Trp53tm1/NIFDC mice administrated with 1000 mg·kg-1 Urethane) and Urethane group 2 (wild type C57BL/6 mice administrated with 1000 mg·kg-1 Urethane). There were 20 mice in each group with 10 male mice and 10 female mice. The body weight, absolute organ weight, relative organ weight, hematological and blood biochemical parameters were measured during and after the test. Statistical analysis was carried out. Results and Conclusion:Compared with negative control group, the body weight of animals in Urethane group 1 and group 2 after 2, 3, 11 and 21 weeks in administration of Urethane decreased greatly. Both the absolute weight of the animals'' lung and spleen in Urethane group 1 and the relative weight of the animals'' lung in Urethane group 1 and Urethane group 2 significantly increased. The levels of NEU, RDW% and CHDW of Urethane group1 and LYM% and BASO% of Urethane group 2 significantly increased. There was no significant change of the blood biochemical parameters in Urethane group 1 and Urethane group 2. |
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| Keywords: | p53+/- knockout mice Urethane organ weight hematological parameters blood biochemical parameters |
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