动脉粥样硬化患者尿液的代谢组学研究

摘要

利用基于液相色谱-质谱联用的方法对动脉粥样硬化( atherosclerosis, AS)患者和正常对照( Control)人群的尿液进行分析,寻找动脉粥样硬化患者尿液中的差异代谢物,为其发病机制及早期筛查提供科学依据。使用VaSera VS-1000无创动脉血管弹性测定仪筛选15名动脉粥样硬化患者(46.84依2.41)及15名健康者(45.72依1.93),采用高分离度快速液相色谱与四极杆-飞行时间串联质谱(RRLC-QTOF/MS)技术对其尿液代谢物进行分析,采用主成分分析( Principal component analysis, PCA)对两组代谢物进行分类,并寻找潜在生物标记物。 RRLC-QTOF/MS检测结果表明,动脉粥样硬化组和对照组尿液代谢物谱能得到很好的区分,发现并鉴定了2种生物标记物尿酸及胍基乙酸,从而提示嘌呤代谢、氨基酸代谢及氧化应激可能在动脉粥样硬化发生发展中有重要作用。%A rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometric ( RRLC-QTOF/MS) method was used to profile the metabolites of urine samples from atherosclerosis ( AS) patients and healthy controls and find the differential metabolites which could provide the scientific evidence to explain the pathogenesis and early disease diagnose. In the study, 15 AS patients ( age46. 84±2. 41 years) and 15 healthy controls ( age45 . 72±1 . 93 years ) was screened out by VaSera VS-1000 . The urine samples were analyzed by RRLC-QTOF/MS and the resulting data matrices were analyzed by multivariate statistical analysis ( Principal Component Analysis, PCA ) to find the potential biomarkers. The results showed that the urine samples of AS patients were successfully distinguished from those of healthy controls. Besides, a total of two significantly changed metabolites, uric acid and Guanidineacetic acid, had been found and identified as potential biomarkers, which suggested that the disorder of purine metabolism and amino acid metabolism played an important role in the mechanism of AS.