脐血流异常对选择性宫内生长受限代谢组学影响的初步探讨

目的:探讨合并脐血流异常对选择性宫内生长受限(s IUGR)脐血血浆代谢组学的影响。方法:纳入6对合并脐血流异常及3对脐血流正常(对照组)的s IUGR双胎,利用气相色谱-飞行时间质谱技术(GC-TOF/MS)对双胎脐血进行代谢物检测,通过主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA)对质谱数据进行多元变量模式识别分析,根据模型的变量投影重要性、学生t检验筛选可能的标记物,并进行代谢通路分析。结果:合并脐血流异常s IUGR筛选出17种有统计学意义的差异代谢物。其中谷氨酸、草酸、环亮氨酸、N-(2-羟乙基)亚氨基二乙酸及L-犬尿氨酸在s IUGR合并脐血流异常组增加,天冬氨酸、N-乙酰-L-天冬氨酸、乳酸、L-苏糖、酪氨酸、甘氨酸、富马酸、β-甘露糖基甘油酸、β-丙氨酸、亚油酸、棕榈酸和马来酰胺酸则降低。结论:GC-TOF/MS方法证实合并脐血流异常的s IUGR代谢组学发生改变,主要体现在脂质、碳水化合物、氨基酸、能量、核酸、辅助因子和维生素代谢等方面。

Preliminary analysis of metabonomics in selective intrauterine growth restriction with abnormal umbilical artery Doppler flow

Objective:To analyze the correlation between umbilical artery (UA) Doppler flow and selective intrauterine growth restriction (sIUGR) cord blood metabolomics.Method:Totally 6 sIUGR with abnormal UA Doppler flow and 3 normal controls were enrolled.Gas chromatography-Time-of-flight mass spectrometry (GC-TOF/MS) was performed on cord blood.Pattern recognition by multivariate analysis including principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) was applied.Several metabolites different between two groups were identified by variable importance in the projection values and Student's t-test,and statistically significant metabolites were subjected to metabolic pathways analysis.Result:Seventeen metabolites were identified.Five variables,including glutamic acid,oxalic acid,cycloleucine,N-(2-hydroxyethyl)-iminodiacetic acid,L-kynurenine,increased significantly,while aspartic acid,N-acetyl-L-aspartic acid,lactic acid,L-Threose,tyrosine,glycine,fumaric acid,beta-Mannosylglycerate,beta-Alanine,linoleic acid,palmitic acid and maleamate were significantly decreased in sIUGR with abnormal UA Doppler flow.Conclusion:GC-TOF/MS can be used to characterize changes in metabolomics of sIUGR with abnormal UA Doppler flow,our data also suggest that metabolic pathways including lipid,carbohydrate,amino acid,energy,nucleotide,as well as cofactors and vitamins metabolism changed.