Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
J Proteome Res. 2013 Sep 6;12(9):4230-9. doi: 10.1021/pr400617m. Epub 2013 Aug 21.
Neonatal hypoxic ischemic encephalopathy (HIE) is a severe consequence of perinatal asphyxia (PA) that can result in life-long neurological disability. Disease mechanisms, including the role and interaction of individual metabolic pathways, remain unclear. As hypoxia is an acute condition, aerobic energy metabolism is central to global metabolic pathways, and these metabolites are detectable using 1H NMR spectroscopy, we hypothesized that characterizing the NMR-derived umbilical cord serum metabolome would offer insight into the consequences of PA that lead to HIE. Fifty-nine at-risk infants were enrolled, together with 1:1 matched healthy controls, and stratified by disease severity (n=25, HIE; n=34, non-HIE PA). Eighteen of 37 reproducibly detectable metabolites were significantly altered between study groups. Acetone, 3-hydroxybutyrate, succinate, and glycerol were significantly differentially altered in severe HIE. Multivariate data analysis revealed a metabolite profile associated with both asphyxia and HIE. Multiple-linear regression modeling using 4 metabolites (3-hydroxybutyrate, glycerol, O-phosphocholine, and succinate) predicted HIE severity with an adjusted R2 of 0.4. Altered ketones suggest that systemic metabolism may play a critical role in preventing neurological injury, while altered succinate provides a possible explanation for hypoxia-inducible factor 1-α (HIF-1α) stabilization in HI injury.
新生儿缺氧缺血性脑病（HIE）是围产期窒息（PA）的严重后果，可导致终身神经功能障碍。疾病机制，包括个体代谢途径的作用和相互作用，仍不清楚。由于缺氧是一种急性情况，有氧能量代谢是全球代谢途径的核心，这些代谢物可以使用 1H NMR 光谱检测，我们假设描述 NMR 衍生的脐带血清代谢组将提供对导致 HIE 的 PA 后果的深入了解。59 名高危婴儿被招募，与 1:1 匹配的健康对照组一起，并按疾病严重程度分层（n=25，HIE；n=34，非 HIE PA）。18 种可重复检测到的代谢物在研究组之间有显著差异。丙酮、3-羟基丁酸、琥珀酸和甘油在严重 HIE 中差异显著改变。多元数据分析揭示了与窒息和 HIE 相关的代谢物特征。使用 4 种代谢物（3-羟基丁酸、甘油、O-磷酸胆碱和琥珀酸）的多元线性回归模型预测 HIE 严重程度的调整 R2 为 0.4。改变的酮表明全身代谢可能在预防神经损伤中起关键作用，而改变的琥珀酸为 HI 损伤中缺氧诱导因子 1-α（HIF-1α）稳定提供了可能的解释。
