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百草枯中毒患者的早期代谢组学分析及其预后价值:基于超高效液相色谱-四极杆飞行时间质谱联用技术

Early Metabolome Profiling and Prognostic Value in Paraquat-Poisoned Patients: Based on Ultraperformance Liquid Chromatography Coupled To Quadrupole Time-of-Flight Mass Spectrometry.

作者信息

Hu Lufeng, Hong Guangliang, Tang Yahui, Wang Xianqin, Wen Congcong, Lin Feiyan, Lu Zhongqiu

机构信息

Department of Pharmacy, The First Affliated Hospital of Wenzhou Medical University , Wenzhou 325000, China.

Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou 325000, China.

出版信息

Chem Res Toxicol. 2017 Dec 18;30(12):2151-2158. doi: 10.1021/acs.chemrestox.7b00240. Epub 2017 Nov 13.

Abstract

Paraquat (PQ) has caused countless deaths throughout the world. There remains no effective treatment for PQ poisoning. Here we study the blood metabolome of PQ-poisoned patients using ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). Patients were divided into groups according to blood PQ concentration. Healthy subjects served as controls. Metabolic features were statistically analyzed using multivariate pattern-recognition techniques to identify the most important metabolites. Selected metabolites were further compared with a series of clinical indexes to assess the prognostic value. PQ-poisoned patients showed substantial differences compared with healthy subjects. Based on variable of importance in the project (VIP) values and statistical analysis, 17 metabolites were selected and identified. These metabolites well-classified low PQ-poisoned patients, high PQ-poisoned patients, and healthy subjects, which was better than that of a complete blood count (CBC). Among the 17 metabolites, 20:3/18:1-PC (PC), LPA (0:0/16:0) (LPA), 19-oxo-deoxycorticosterone (19-oxo-DOC), and eicosapentaenoic acid (EPA) had prognostic value. In particular, EPA was the most sensitive one. Besides, the levels of EPA was correlated with LPA and 19-oxo-DOC. If EPA was excessively consumed, then prognosis was poor. In conclusion, the serum metabolome is substantially perturbed by PQ poisoning. EPA is the most important biomarker in early PQ poisoning.

摘要

百草枯(PQ)在全球已导致无数人死亡。目前仍没有针对PQ中毒的有效治疗方法。在此,我们使用超高效液相色谱-四极杆飞行时间质谱联用技术(UPLC/Q-TOF MS)研究PQ中毒患者的血液代谢组。根据血液中PQ浓度将患者分组。健康受试者作为对照。使用多变量模式识别技术对代谢特征进行统计分析,以确定最重要的代谢物。将选定的代谢物与一系列临床指标进一步比较,以评估其预后价值。与健康受试者相比,PQ中毒患者表现出显著差异。基于项目中变量重要性(VIP)值和统计分析,选择并鉴定了17种代谢物。这些代谢物能很好地将低PQ中毒患者、高PQ中毒患者和健康受试者区分开来,其区分效果优于全血细胞计数(CBC)。在这17种代谢物中,20:3/18:1-PC(PC)、LPA(0:0/16:0)(LPA)、19-氧代-脱氧皮质酮(19-oxo-DOC)和二十碳五烯酸(EPA)具有预后价值。特别是,EPA是最敏感的一种。此外,EPA的水平与LPA和19-oxo-DOC相关。如果EPA过度消耗,则预后不良。总之,血清代谢组因PQ中毒而受到显著干扰。EPA是早期PQ中毒最重要的生物标志物。

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