抗肿瘤化合物Z24对Wistar大鼠灌胃给药5d的尿液代谢时间轨迹研究  

Metabolic trajectory analysis of urine from Wistar rats orally administrated for 5 days with Z24,a novel anti-tumor agent

作　　者：王全军[1] 吴纯启[1] 颜贤忠[2] 赵剑宇[2] 余寿忠[1] 袁本利[1] 廖明阳[1] 

机构地区：[1]军事医学科学院毒物药物研究所,国家北京药物安全评价研究中心,北京100850 [2]国家生物医学分析中心,北京100850

出　　处：《中国新药杂志》2008年第3期203-206,共4页Chinese Journal of New Drugs

基　　金：国家高技术研究发展计划(863计划)资助(2002AA2Z342D)

摘　　要：目的:研究机体代谢时间轨迹改变与机体血液生化和组织病理学检查的关系,确定使用代谢组学技术研究毒性发生发展的可行性。方法:抗肿瘤化合物Z24以130 mg.kg-1剂量对W istar大鼠连续灌胃给药5 d,分别在给药前、给药过程中和停药后,收集24 h的尿液,一直收集到停药后240 h,尿液用于代谢组学研究。在停药后24 h和240 h时分别处死一半大鼠进行病理和血液生化检测。结果:代谢时间轨迹改变与血液生化和组织病理学的改变具有一定的相关性。结论:代谢组学技术可应用于描述毒性的发生、发展和恢复过程。Objective：To study the relationship between the time-related changes in the IH NMR spectral profile and the changes in blood biochemistry and histopathology, so to evaluate the feasibility to monitor the toxicity development using metabonomic techniques. Methods： In Wistar rats, the anti-tumor agent Z24 （130 mg·kg^-1） were orally administered for 5 days. For metabonomic analysis, the 24-h urine samples were collected before, during and after dosing until to 240 h after withdrawal. At 24 h and 240 h after withdrawal, half of rats were killed, respectively, for blood biochemical analysis and liver histopathological examination. Results： There was dependability relationship between the time-related changes in metabolic trajectory and the changes in blood biochemical analysis and liver histopathological examination. Conclusion ： The phases of toxicity generation, development and recovery can be described by the metabonomic technique.

关 键 词：Z24 大鼠 代谢组学 代谢轨迹 

分 类 号：R969.2[医药卫生—药理学] R979.1[医药卫生—药学]