基于质谱技术的早产儿与足月儿尿代谢组学研究

Urinary metabonomics research based on mass spectrometry in preterm and term infants

目的 应用气相色谱-质谱和代谢组学方法研究早产儿和足月儿尿代谢产物的差异,寻找早产儿尿液中特异的生物标志物.方法 收集中山大学附属第六医院30例早产儿和20例足月儿的尿液标本,利用气相色谱-质谱技术测定葡萄糖、乳糖、乳酸、甘油、软脂酸、硬脂酸、缬氨酸、亮氨酸、异亮氨酸、甘氨酸、丙氨酸、苏氨酸、阿拉伯糖醇、木糖、乙酰天门冬氨酸等173种尿代谢产物水平,并应用主成分分析（PCA）和偏最小二乘判别分析（PLS）寻找2组间的差异和生物标志物.结果 1.早产儿尿代谢产物和足月儿有明显的差异,PLS累计解释率R2 Xcum=0.592,预测累计解释率R2 Ycum=0.972,交互校验的复相关系数Q2cum =0.959,利用PCA和PLA可对2组进行判别;2.PCA发现早产儿与足月儿的特异性代谢产物（生物标志物）为硬脂酸、乳酸;3.早产儿与足月儿在氨基酸（缬氨酸、亮氨酸、异亮氨酸、苏氨酸、丙氨酸和甘氨酸）、脂肪（甘油、软脂酸、硬脂酸）和糖（乳糖、乳酸）代谢通路中的主要代谢产物均具有明显差异.结论 早产儿与足月儿代谢产物具有明显差异,应用色谱-质谱测定尿代谢产物结合代谢组学分析方法可作为评估新生儿体内代谢状况的重要手段,对纠正早产儿体内代谢紊乱、合理补充营养物质具有重要意义.

Objective Using gas chromatography-mass spectrometry and metabonomics technique to analyze the difference of urinary metabolites in preterm and term infants,looking for specific biomarkers in the urine of preterm infants.Methods Urine liquid specimens of 30 preterm infants and 20 term children were collected from the sixth Affiliated Hospital of Sun Yat-sen University,using gas chromatography-mass spectrometry technology to determine glucose,lactose,lactic acid,glycerol,palmitic acid,stearic acid,valsartan ammonia acid,light ammonia acid,different light ammonia acid,Gan ammonia acid,c ammonia acid,su ammonia acid,Arab sugar alcohol,wood sugar,and acetyl aspartate ammonia acid and other urine metabolism product content,and using main components analysis（PCA） and partial minimum Ⅱ discriminant analysis （PLS） to look for differences and biomarkers between the 2 groups.Results 1.There was significant difference between preterm infants urine metabolism product and term children,using PCA and PLA discriminant analysis on the 2 groups for discrimination;2.Main components analysis detected preterm infants and term children of special heterosexual metabolism product（biological signs property） for stearic acid,and lactic acid;3.Preterm infants and term children were significantly different in metabolic pathways of major metabolites of amino acids （valsartan ammonia acid,light ammonia acid,different light ammonia acid,Su ammonia acid,c ammonia acid and Gan ammonia acid）,and fat（glycerol,palmitic acid,and stearic acid） and sugar（lactose,and lactic acid）.Conclusions Metabolite has an obvious difference in preterm and term infants,and determination of urine metabolites by gas chromatography-mass spectrometry with metabonomics analysis can be used as important tools to evaluate neonatal metabolic conditions,and is of importance in correcting metabolic disorders in premature infants,and supplying reasonable nutrient substance.