应用串联质谱技术区别早产儿与足月儿血代谢组学生物标志物

Differentiate the biomarkers between preterm and term newborns with the application of tandem mass spectrometry

目的应用串联质谱和代谢组学方法研究早产儿和足月儿血代谢产物的差异，寻找早产儿血代谢特异的生物标志物。方法收集2014年1月至12月中山大学附属第六医院46例早产儿（早产儿组）和55例足月儿（足月儿组）足跟末梢血液标本，利用串联质谱技术及定量软件测定血样本中氨基酸、脂酰肉碱等代谢产物水平，应用正交偏最小二乘判别分析法对早产儿和足月血代谢产物进行代谢组分析，并寻找重要的生物标记物。结果早产儿组和足月儿组血代谢谱比较有统计学差异，在此模式识别过程结合代谢物得分图和权重图分析发现12个权重较大的物质，其中游离肉碱、丁二酰基肉碱、豆蔻酰基肉碱、棕榈酰基肉碱、棕榈烯酰基肉碱、十八碳酰基肉碱、十八碳烯酰基肉碱、甘氨酸、组氨酸和谷氨酸10种物质在早产儿组中降低；异戊酰基肉碱和精氨酸在早产儿组升高。结论与足月儿组相比，早产儿组具有明显不同的血代谢谱，应用串联质谱技术结合代谢组学分析可作为评估新生儿代谢情况的重要方法，筛选到的重要生物标记物对进一步纠正早产儿代谢紊乱、并合理补充营养具有重要价值。

Objective To determine the difference in metabolomics profiles between the preterm and the term newborns, and to search for special biomarker by the application of tandem chromatograph-mass spectrometry and metabolomics.Methods The heel peripheral blood samples were collected from 46 preterm newborns and 55 term newborns（term newborns group） in the Sixth Affiliated Hospital of Sun Yat-Sen University from January to December 2014.The Tandem Mass Spectometry（MS/MS） was used to generate the metabolic fingerprints of amino acid and acyl-carnitine from the heel peripheral blood.The data collected were subjected to the metabolomics analysis by using the orthogonal partial least squares discriminant analysis to search for the considerable biomarkers.Results Heel peripheral plasma from the preterm newborns group and the term newborns group displayed a clearly differentiated metabolic profiles.Twelve metabolites were identified which possessed the biggest weight discriminating the preterm from the term newborns group in the pattern of recognizing process combined with the metabolites score plot with variable importance plot.The preterm newborns group had the lower levels of free carnitine, succinyl carnitine, tetradecanoyl carnitine; palmitoyl carnitine, hexedecenoyl carnitine, stearyl carnitine, oleyl carnitine, glycine, histidine, and glutamic acid than the term newborns group, while plasma levels of isovaleryl carnitine, arginine were higher in the preterm newborns.Conclusions There was a significant difference in metabolomics profiles between the preterm newborns group and the term newborns group.The analysis of MS/MS combined with metabolomics could be essential for evaluating neonatal metabolic status.Besides, the identified biomarkers were of great value in the further study about correcting metabolic disorders and supplying reasonable nutrition in the early life.