基于液相质谱技术探讨阿霉素诱导扩张型心肌病潜在血浆标志物  

Potential plasma biomarkers of adriamycin-induced dilated cardiomyopathy based upon UHPLC-MS/MS

作　　者：李峥[1,4] 杨祎[1] 李明阳 李思琦[2] 孙行 张哲[3] 杨关林[3] 李文杰[4] 张明雪[1] LI Zheng;YANG Yi;LI Ming-yang;LI Si-qi;SUN Hang;ZHAGN Zhe;YANG Guan-lin;LI Wen-jie;ZHANG Ming-xue(First Clinical College,Liaoning University of Traditional Chinese Medicine,Liaoning Sheny ang 110000,China;Affliated Hospital,Liaoning University of Traditional Chinese Medicine,Office of Regional Medical Center,Liaoning Shenyang 11OOOO,China;Liaoning University of Traditional Chinese Medicine,Traditional Chinese Medicine Center of Innovation&Engineering,Liaoning Shenyang 110000,China;Department of Cardiology,Affiliated Hospital,Liaoning University of Traditional Chinese Medicine,Liaoning Shenyang 11OOOO,China)

机构地区：[1]辽宁中医药大学第一临床学院,辽宁沈阳110000 [2]辽宁中医药大学附属医院区域诊疗中心办公室,辽宁沈阳110000 [3]辽宁中医药大学中医药创新工程中心,辽宁沈阳110000 [4]辽宁中医药大学附属医院心内科,辽宁沈阳110000

出　　处：《中国医院药学杂志》2021年第16期1617-1624,共8页Chinese Journal of Hospital Pharmacy

基　　金：辽宁省科技厅项目(编号:2020-BS-165);沈阳市科技厅项目(编号:19-112-4-059)。

摘　　要：目的:扩张性心肌病是应用阿霉素治疗肿瘤的严重副作用之一,致死率可达50%。通过建立阿霉素扩张型心肌病动物模型对比健康动物,寻找该疾病的生物标志物。方法:采用阿霉素注射法制备扩张型心肌病模型,造模后收集模型组与对照组大鼠的血浆与心肌组织,应用液相质谱技术检测血浆及心肌代谢物,选择共同存在于血浆及心肌组织中的代谢物,并应用ROC曲线进行血浆标志物的筛选。结果:得到45种共同存在于血浆和心肌组织中的差异性代谢物,其中22种代谢物的ROC曲线下面积值(area under the ROC curve,AUC)为1,最佳阈值下的特异性与敏感性均为1。结论:2’-脱氧尿苷等22种差异代谢物对于阿霉素诱导出的中毒性扩张型心肌病具有较强的潜在诊断价值,可能是潜在的生物标志物。OBJECTIVE Dilated cardiomyopathy is one of the severe side effects for adriamycin in the treatment of cancers.The mortality rate was as high as 50%.Biomarkers were searched by comparing animals in control and adiramycin-induced cardiomyopathy groups.METHODS Animals in adiramycin-induced cardiomyopathy group received an injection of adriamycin.Plasma and cardiac tissue were collected when animals in adiramycin-induced cardiomyopathy group were diagnosed with dilated cardiomyopathy.Liquid chromatography-mass spectrometry was utilized for examining metabolites and ROC curve was plotted for selecting biomarkers.RESULTS A total of 45 metabolites were discovered both in plasma and cardiac tissue.And 22 of them had an AUC value of 1 as well as great specificity and sensitivity.CONCLUSION With potent diagnostic values,these 22 metabolites,including deoxyuridine,may become potential biomarkers for adriamycin-induced dilated cardiomyopathy.

关 键 词：阿霉素 扩张型心肌病 血浆标志物 代谢组 心肌组织 

分 类 号：R917[医药卫生—药物分析学]