中国药理学通报2012,Vol.28Issue(9):1294-1299,6.DOI:10.3969/j.issn.1001-1978.2012.09.025
基于血清代谢组学的吡柔比星注射剂的累积毒性作用研究
Serum metabolites of commerical pirarubicin injections
摘要
Abstract
Aim To investigate the cumulative toxicity of commercial pirarubicin injection after 2 intravenous administrations on the normal sprague-dawley rats with serum metabonomics. Methods The metabolic profiles of serum sample were obtained with ultra performance liquid chromatography coupled with time-of-flight mass spectrometry ( UPLC/TOF-MS ). The data were further processed with Masslynx software and analyzed with partial least squares discriminate analysis ( PLS-DA ). On the basis of a VIP ( variable importance in projection ) threshold of 1 from the 7-fold cross-validated PLS-DA model and student' s test, potential biomark-ers responsible for the difference in the metabolic profiles were obtained. Finally , they were identified by authentic standards or available databases. Results It could be found that multiple dosages of THP would lead to fatty acids and phospholipids disturbance and severe cardiotoxicity via adriamycinone through the reactive oxygen species ( ROS ) mechanism. Conclusion This study can provide a basis for the potential bio- markers screening of the cumulative cardiotoxicity of commercial pirarubicin injection in clinic.关键词
吡柔比星注射剂/代谢组学/血清/累积毒性/作用机制/蒽环类抗生素Key words
pirarubicin injection/ metabonomics/ serum/ cumulative toxicity/ mechanism study/ anthracy-cline分类
医药卫生引用本文复制引用
从文娟,刘清飞,梁琼麟,罗国安,阮克锋,冯怡..基于血清代谢组学的吡柔比星注射剂的累积毒性作用研究[J].中国药理学通报,2012,28(9):1294-1299,6.基金项目
国家自然科学基金资助项目(No 81173516) (No 81173516)
上海市高校青年教师专项基金资助项目(No shzy013) (No shzy013)