基于超高效液相色谱-高分辨质谱(UPLC-HRMS)联用技术建立了全扫描/数据依赖型采集(Full MS/ddMS2)模式和全扫描/平行反应监测(Full MS/PRM)模式相结合的血浆酰基肉碱定性和定量分析方法,共定性分析了165种酰基肉碱,定量分析了111种酰基肉碱.本方法重复性好,血浆酰基肉碱含量的相对标准偏差均小于20%.t检验、偏最小二乘-判别分析、变量重要性投影和火山图分析等结果表明,心梗后心衰患者的血浆酰基肉碱水平发生显著变化,其中46种酰基肉碱含量较心梗患者显著上升.酰基肉碱与心衰的临床生物学标志物NT-proBNP含量呈显著正相关,通过对酰基肉碱指标AC(C14-OH)、AC(C12∶1a)、长链酰基肉碱、总酰基肉碱和NT-proBNP的联合分析可大大提高心梗后心衰诊断的灵敏度和特异度,受试者工作特征曲线下面积(Area under curve,AUC)值提升至0.9456.酰基肉碱有望成为心梗后心衰精准诊断及疾病发展进程中治疗和营养干预的重要代谢靶标.
A Targeted Metabolomic Study of Plasma Acylcarnitines in Patients with Myocardial Infarction and Heart Failure after Myocardial Infarction
A combined full-scan mass spectrometry/data-dependent acquisition(Full MS/ddMS2)and full-scan mass spectrometry/parallel reaction monitoring(Full MS/PRM)approach for qualitative and quantitative analysis of plasma acylcarnitines was established on the basis of ultra-performance liquid chromatography-high resolution mass spectrometry(UPLC-HRMS).A total of 165 kinds of acylcarnitines were identified,and 111 kinds of acylcarnitines were quantified.The method demonstrated good reproducibility,with a relative standard deviation of less than 20%for plasma acylcarnitine content.Statistical analyses,including t-tests,partial least squares-discriminant analysis,variable importance in projection and volcano plot analysis,indicated significant alterations in plasma acylcarnitine levels in heart failure patients after myocardial infarction,for instance,46 kinds of acylcarnitines showing marked increases compared to myocardial infarction patients.Acylcarnitines showed a strong positive correlation with the clinical biomarker NT-proBNP,which was associated with heart failure.The combined use of acylcarnitine markers AC(C14-OH),AC(C12:1a),long-chain acylcarnitines,total acylcarnitines and NT-proBNP significantly enhanced the diagnostic sensitivity and specificity for post-infarction heart failure,with the area under the receiver operating characteristic curve(AUC)reaching 0.9456.The results of this work indicated that acylcarnitine was poised to become a crucial metabolic target for precise diagnosis,treatment and nutritional intervention in the progression of heart failure after myocardial infarction.
AcylcarnitinesUltra-performance liquid chromatography-high resolution mass spectrometryMyocardial infarctionHeart failureMetabolomics
国家科技期刊平台
NSTL
万方数据
