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基于代谢平衡模型评价阿霉素在大鼠体内的心脏毒性

江慧勇, 严颐丹, 刘昊辰, 郑运思, 王艺璇, 何华, 柳晓泉

江慧勇, 严颐丹, 刘昊辰, 郑运思, 王艺璇, 何华, 柳晓泉. 基于代谢平衡模型评价阿霉素在大鼠体内的心脏毒性[J]. 中国药科大学学报, 2015, 46(2): 224-229. DOI: 10.11665/j.issn.1000-5048.20150215
引用本文: 江慧勇, 严颐丹, 刘昊辰, 郑运思, 王艺璇, 何华, 柳晓泉. 基于代谢平衡模型评价阿霉素在大鼠体内的心脏毒性[J]. 中国药科大学学报, 2015, 46(2): 224-229. DOI: 10.11665/j.issn.1000-5048.20150215
JIANG Huiyong, YAN Yidan, LIU Haochen, ZHENG Yunsi, WANG Yixuan, HE Hua, LIU Xiaoquan. Evaluation of cardiotoxicity of doxorubicin in rat by a novel metabolic balance model[J]. Journal of China Pharmaceutical University, 2015, 46(2): 224-229. DOI: 10.11665/j.issn.1000-5048.20150215
Citation: JIANG Huiyong, YAN Yidan, LIU Haochen, ZHENG Yunsi, WANG Yixuan, HE Hua, LIU Xiaoquan. Evaluation of cardiotoxicity of doxorubicin in rat by a novel metabolic balance model[J]. Journal of China Pharmaceutical University, 2015, 46(2): 224-229. DOI: 10.11665/j.issn.1000-5048.20150215

基于代谢平衡模型评价阿霉素在大鼠体内的心脏毒性

基金项目: 国家自然科学基金资助项目(No.81273588,No.81473274)

Evaluation of cardiotoxicity of doxorubicin in rat by a novel metabolic balance model

  • 摘要: 采用代谢平衡模型从整体角度评价阿霉素心脏毒性。大鼠随机分为3组,分别为对照组、低剂量(累积剂量8 mg/kg)和高剂量组(累积剂量15 mg/kg),分别于第1、4、7、10天腹腔注射给药并在不同时间点采集血样,测定血浆中的一氧化氮(NO)、B型脑钠肽(BNP)的含量以及谷胱甘肽过氧化物酶(GSH-Px)和黄嘌呤氧化酶(XOD)的酶活力,基于上述标记物建立代谢平衡模型,用于评价阿霉素的心脏毒性。代谢平衡相图和代谢失衡动力学参数的结果提示,阿霉素导致体内多个生物标记物发生明显改变,引起代谢失衡,且代谢失衡的程度与射血分数(ejection fraction,EF)之间具有良好相关性。代谢平衡模型为整体评价阿霉素诱导的心脏毒性提供了一种新的思路和方法。
    Abstract: The study developed a metabolic balance model to evaluated the cardiotoxicity of doxorubicin. The rats were divided into 3 groups, control group(saline), low dose group(8 mg/kg of cumulative doxorubicin)and high dose group(15 mg/kg of cumulative doxorubicin). Doxorubicin or saline was intraperitoneally injected and blood sample was collected at day 1, 4, 7 and 10. The concentrations of nitric oxide(NO), B-type natriuretic peptide(BNP)and the activity of glutathion peroxidase(GSH-Px), xanthine oxidase(XOD)in rat plasma were determined. A metabolic balance model based on the four biomarkers was developed to evaluate the doxorubicin cardiotoxicity in rat. Doxorubicin leaded to significant changes of multiple biomarkers, resulting in metabolic balance disruption according to the metabolic balance maps and dynamic parameters of metabolic balance disruption. Moreover, the correlation study showed a good relationship between metabolic balance disruption and ejection fraction(EF). The metabolic balance model provide a novel method to integrally evaluate the doxorubicin-induced cardiotoxicity.
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  • 刊出日期:  2015-04-24

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