慢性心功能衰竭患者尿液的代谢组学研究

Metabonomics Study of Chronic Heart Failure by Rapid Resolution Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry

采用基于液相色谱-质谱联用的方法对慢性心力衰竭(Chronic heart failure,CHF)患者和正常对照(Control)人群的尿液进行分析,筛选慢性心力衰竭患者尿液中的差异代谢物,研究其发病机制,并为临床治疗提供科学依据。选择15个慢性心力衰竭患者(年龄(62.27±3.14)岁)及15个正常人(年龄(65.41±4.63)岁),采用高分辨度快速液相色谱-四极杆-飞行时间串联质谱(RRLC-QTOF/MS)技术对尿液代谢物进行分析,采用主成分分析(PCA)对两组代谢物进行分类,并筛选潜在生物标记物;运用偏最小二乘判别分析法(PLS-DA)建模,考察生物标记物对疾病筛选的预测能力。研究结果表明,CHF组和Control组尿液代谢物谱能得到很好的区分,发现并鉴定了2种潜在生物标记物尿苷及丙氨酰色氨酸,提示嘧啶代谢和色氨酸代谢可能在心力衰竭发生发展中有重要作用。

In this study, the rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry （ RRLC-QTOF/MS） was used to profile the metabolites of urine samples from chronic heart failure （ CHF） patients and healthy controls to find the differential metabolites which could provide the scientific evidence to explain the pathogenesis of the disease and supply a better therapy plan. Urine samples from 15 CHF patients （age （62. 27±3. 14） years） and 15 healthy controls （age （65. 41 ±4. 63） years） were analyzed by RRLC-QTOF/MS. After processing the data, the multivariate statistical analysis （ principal component analysis, PCA） was performed to find the potential biomarkers. Result showed that urine samples of CHF patients were successfully distinguished from those of healthy controls. Two significantly differentially expressed metabolites, uridine and alanyltryptophan, were found and identified as potential biomarkers. The result showed that the LC-MS based metabolomics approach had good performance to identify potential biomarkers, and the disorder of uracil metabolism and Tryptophan metabolism may play an important role in the mechanism of CHF.