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产前疾病对中期羊水代谢特征的影响:基于核磁共振代谢组学的研究。

Impact of prenatal disorders on the metabolic profile of second trimester amniotic fluid: a nuclear magnetic resonance metabonomic study.

机构信息

CICECO-Department of Chemistry, Campus Universitário de Santiago, Universidade de Aveiro, Aveiro, Portugal.

出版信息

J Proteome Res. 2010 Nov 5;9(11):6016-24. doi: 10.1021/pr100815q. Epub 2010 Oct 11.

Abstract

This paper describes a metabonomic study of prenatal disorders using nuclear magnetic resonance (NMR) spectroscopy of amniotic fluid (AF) collected in the second trimester of pregnancy, to search for metabolite markers of fetal malformations, prediagnostic gestational diabetes (GD), preterm delivery (PTD), early rupture of membranes (PROM), and chromossomopathies. Fetal malformations were found to have the highest impact on AF metabolite composition, enabling statistical validation to be achieved by several multivariate analytical tools. Results confirmed previous indications that malformed fetuses seem to suffer altered energy metabolism and kidney underdevelopment. Newly found changes (namely in α-oxoisovalerate, ascorbate, creatinine, isoleucine, serine, threonine) suggest possible additional effects on protein and nucleotide sugar biosynthesis. Prediagnostic GD subjects showed an average increase in glucose and small decreases in several amino acids along with acetate, formate, creatinine, and glycerophosphocholine. Small metabolite changes were also observed in the AF of subjects eventually undergoing PTD and PROM, whereas no relevant changes were found for chromossomopathies (for which a low number of samples was considered). The potential value of these results for biochemical insight and prediction of prenatal disorders is discussed, as well as their limitations regarding number of samples and overlap of different disorders.

摘要

本文描述了一项使用核磁共振(NMR)光谱技术对妊娠中期羊水进行代谢组学研究的产前疾病研究,以寻找胎儿畸形、产前诊断性妊娠糖尿病(GD)、早产(PTD)、胎膜早破(PROM)和染色体病的代谢标志物。研究发现,胎儿畸形对羊水代谢物组成的影响最大,通过几种多元分析工具实现了统计验证。结果证实了先前的研究结果,即畸形胎儿似乎存在能量代谢异常和肾脏发育不全。新发现的变化(即α-氧代异戊酸、抗坏血酸、肌酸、异亮氨酸、丝氨酸、苏氨酸)提示可能对蛋白质和核苷酸糖的生物合成有其他影响。产前诊断性 GD 患者的葡萄糖水平平均升高,同时伴有几种氨基酸以及乙酸盐、甲酸盐、肌酸和甘油磷酸胆碱的小幅度降低。最终发生 PTD 和 PROM 的受试者的羊水也观察到了较小的代谢物变化,而染色体病则没有发现相关变化(考虑到样本数量较少)。本文讨论了这些结果在生化研究和产前疾病预测方面的潜在价值,以及样本数量和不同疾病重叠对结果的限制。

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