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基于液相色谱-质谱联用的代谢组学鉴定绒毛膜羊膜炎及其相关围产期神经损伤的新型生物标志物

LC-MS-based metabolomics identification of novel biomarkers of chorioamnionitis and its associated perinatal neurological damage.

作者信息

Dudzik Danuta, Revello Rocio, Barbas Coral, Bartha Jose L

机构信息

CEMBIO (Center for Metabolomics and Bioanalysis), Pharmacy Faculty, University San Pablo CEU , 28668 Madrid, Spain.

出版信息

J Proteome Res. 2015 Mar 6;14(3):1432-44. doi: 10.1021/pr501087x. Epub 2015 Feb 13.

DOI:10.1021/pr501087x
PMID:25620495
Abstract

Chorioamnionitis is a complication of pregnancy associated with significant maternal and perinatal long-term adverse outcomes. We apply high-throughput amniotic fluid (AF) metabolomics analysis for better understanding the pathophysiological mechanism of chorioamnionitis and its associated perinatal neurological injury and to provide meaningful information about new potential biomarkers. AF samples (n = 40) were collected from women at risk of chorioamnionits. Detailed clinical information on each pregnancy was obtained from obstetrical and neonatal medical examination. Liquid chromatography (LC)/mass spectrometry (MS) followed by data alignment and filtration as well as univariate and multivariate statistical analysis was performed. Statistically significant differences were found in 60 masses in positive and 115 in negative ionization mode obtained with LC/quadrupole time-of-flight MS (LC-QTOF-MS) between women with and without chorioamnionitis. Identified compounds were mainly related to glycerophospholipids and sphingolipids metabolism. From them, LPE(16:0)/LPE(P-16:0) and especially lactosylceramides emerged as the best biomarker candidates. Sulfocholic acid, trioxocholenoic acids, and LPC(18:2) were particularly increased in women with chorioamnionitis whose newborns developed perinatal brain damage. Therefore, we propose LPE(16:0)/LPE(P-16:0) and lactosylceramides as biomarkers for chorioamnionitis as well as LPC(18:2), trioxocholenoic acid, and sulfocholic acid for its associated perinatal brain damage. Metabolomics fingerprinting of AF enables the prediction of pregnancy-related disorders and the development of new diagnostics strategies.

摘要

绒毛膜羊膜炎是一种与孕产妇和围产期长期不良结局相关的妊娠并发症。我们应用高通量羊水(AF)代谢组学分析,以更好地了解绒毛膜羊膜炎的病理生理机制及其相关的围产期神经损伤,并提供有关新的潜在生物标志物的有意义信息。从有绒毛膜羊膜炎风险的女性中收集AF样本(n = 40)。从产科和新生儿医学检查中获取每次妊娠的详细临床信息。进行液相色谱(LC)/质谱(MS)分析,随后进行数据比对和过滤以及单变量和多变量统计分析。在患有和未患有绒毛膜羊膜炎的女性中,通过LC/四极杆飞行时间质谱(LC-QTOF-MS)在正离子模式下发现60个质量峰存在统计学显著差异,在负离子模式下发现115个质量峰存在统计学显著差异。鉴定出的化合物主要与甘油磷脂和鞘脂代谢有关。其中,LPE(16:0)/LPE(P-16:0),尤其是乳糖神经酰胺成为最佳的生物标志物候选物。患有绒毛膜羊膜炎且其新生儿发生围产期脑损伤的女性中,磺胆酸、三氧胆烯酸和LPC(18:2)尤其升高。因此,我们提出LPE(16:0)/LPE(P-16:0)和乳糖神经酰胺作为绒毛膜羊膜炎的生物标志物,以及LPC(18:2)、三氧胆烯酸和磺胆酸作为其相关围产期脑损伤的生物标志物。羊水的代谢组学指纹图谱能够预测与妊娠相关的疾病并开发新的诊断策略。

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