Li S T, Huang X L, Wu S G, Ma Y M, Shi C C, Xiao X, Hao H
Department of Pediatrics, the Sixth Affiliated Hospital of Sun Yet-Sen University, Guangzhou 510655, China.
Zhonghua Er Ke Za Zhi. 2017 Jun 2;55(6):434-438. doi: 10.3760/cma.j.issn.0578-1310.2017.06.008.
To investigate the urinary metabolic spectrum and pathways in very low birth weight (VLBW) premature infants. A prospective case-control study was conducted to collect and compare the data of VLBW premature infants and full term infants from the Sixth Affiliated Hospital of Sun Yet-Sen University in 2014. Within 24 hours after birth, urine specimens in each group were collected. Metabolites of urine samples including amino acid, fatty acid and organic acid were detected using the urease pre-processing and gas chromatography mass spectrometry (GC-MS) technology. Using the orthogonal partial least squares discriminant analysis (OPLS-DA), the biomarkers and differences between the two groups were found. The online metabolic pathway website was explored and multivariable analysis was conducted to investigate the valuable pathways and biomarkers related to the prematurity. A total of 20 VLBW premature infants were enrolled, among whom 11 were male, 9 were female; and 20 full term infants were enrolled, among whom 9 were male, 11 were female. The urinary metabolites were established and compared between the VLBW premature and term infants. The investigation showed that the following nine pathways were enriched: amino-acyl-tRNA biosynthesis(=0.000), lysine degradation(=0.007), fatty acid biosynthesis(=0.008), pyrimidine metabolism(=0.014), pantothenate and CoA biosynthesis(=0.022), valine, leucine and isoleucine biosynthesis(=0.022), lysine biosynthesis(=0.031), glycerolipid metabolism(=0.046), and valine, leucine and isoleucine degradation(=0.031). Almost all the metabolites decreased except for the glyceric acid exhibiting a higher content in the VLBW premature infant. 12 potential biomarkers were explored with the most significant covariance and correlation, within which stearic acid, palmiticacid, myristic acid, β-amino-isobutyric acid, and uric acid were lower, while myo-inositol, mannitol, glycine, glucose1, glucose2, glyceric acid and N-acetyl-tyrosine were higher in the VLBW premature group compared with the control group. There is a significant difference between the VLBW premature infants and full-term infants in the metabolic state and pathways. The urease pre-processing and GC-MS technology followed by the OPLS-DA and multivariable analysis to investigate VLBW premature infants' urinary metabolites is a valuable method to evaluate the patients' metabolism.
探讨极低出生体重（VLBW）早产儿的尿液代谢谱及代谢途径。开展一项前瞻性病例对照研究，收集并比较2014年中山大学附属第六医院VLBW早产儿和足月儿的数据。在出生后24小时内，收集每组的尿液标本。采用尿素酶预处理和气相色谱 - 质谱联用（GC-MS）技术检测尿液样本中的氨基酸、脂肪酸和有机酸等代谢物。运用正交偏最小二乘法判别分析（OPLS-DA），找出两组之间的生物标志物及差异。探索在线代谢途径网站并进行多变量分析，以研究与早产相关的有价值途径和生物标志物。共纳入20例VLBW早产儿，其中男11例，女9例；纳入20例足月儿，其中男9例，女11例。建立并比较了VLBW早产儿和足月儿的尿液代谢物。研究表明，以下九条途径富集：氨酰 - tRNA生物合成（=0.000）、赖氨酸降解（=0.007）、脂肪酸生物合成（=0.008）、嘧啶代谢（=0.014）、泛酸和辅酶A生物合成（=0.022）、缬氨酸、亮氨酸和异亮氨酸生物合成（=0.022）、赖氨酸生物合成（=0.031）、甘油olipid代谢（=0.046）以及缬氨酸、亮氨酸和异亮氨酸降解（=0.031）。除甘油酸在VLBW早产儿中含量较高外，几乎所有代谢物均降低。探索出12种具有最显著协方差和相关性的潜在生物标志物，与对照组相比，VLBW早产组中硬脂酸、棕榈酸、肉豆蔻酸、β-氨基异丁酸和尿酸较低，而肌醇、甘露醇、甘氨酸、葡萄糖1、葡萄糖2、甘油酸和N-乙酰酪氨酸较高。VLBW早产儿与足月儿在代谢状态和途径上存在显著差异。采用尿素酶预处理和GC-MS技术，随后进行OPLS-DA和多变量分析来研究VLBW早产儿的尿液代谢物，是评估患者代谢的一种有价值方法。
