基于代谢组学方法的小儿肺炎易感性研究  

Metabolomics Study on Susceptibility of Pneumonia in Children

作　　者：林丽丽[1,2,3] 汪受传 杨燕[4] 谢彤[1,2] 赵霞 任靖[1,2,3] 李维薇[1,2,3] 陶嘉磊 范嗣立[5] 单进军 

机构地区：[1]江苏省儿童呼吸疾病(中医药)重点实验室,南京中医药大学中医儿科学研究所,南京210023 [2]南京中医药大学医学代谢组学中心,南京210023 [3]南京中医药大学附属医院,南京210029 [4]首都医科大学附属北京儿童医院,北京100045 [5]Genome Center of UC Davis,NIH West Coast Metabolomics Center,Davis 95616,USA

出　　处：《分析化学》2018年第2期188-194,共7页Chinese Journal of Analytical Chemistry

基　　金：本文系国家自然科学基金项目(No.81373688)、江苏省研究生培养创新工程(No.SJLX_0432)、江苏省“333工程冶科研资助项目(No.BRA2016427)和江苏省“六大人才高峰冶高层次人才选拔培养项目(No.YY鄄022)资助

摘　　要：以6个月到6岁肺炎患儿尿液为样本,采用基于气相色谱与质谱联用技术(GC-MS)的代谢组学方法,研究肺炎患儿尿液内源性代谢产物的变化及其易感性的发病机制。收集不同感染次数的肺炎患儿尿液样本,包括正常儿童组29例、单次感染肺炎患儿组35例、多次感染肺炎患儿组31例,分析获得肺炎患儿尿液代谢轮廓;同时对所得数据进行主成分分析(PCA)及偏最小二乘法-判别分析(PLS-DA)等多元统计分析,综合单因素方差分析及倍数(Fold change,FC)变化分析结果,最终筛选并通过Fiehn-Lib等数据库鉴定丝氨酸、组氨酸、脯氨酸、正亮氨酸、谷氨酰胺、硬脂酸、缬氨酸和异亮氨酸、乳糖醛酸等在正常儿童组与肺炎患儿组之间有代谢差异(p value adjusted by FDR<0.05)且FC>5,吲哚-3-乙酸、肌酸、乙醇胺、甘露糖基甘油酸和果糖在不同感染次数肺炎组之间具有差异性(p value adjusted by FDR<0.05)。实验结果表明,肺炎患儿易感性体质存在差异性代谢物,这些代谢物主要通过氨基酸及糖代谢对肺炎易感性产生影响。The changes of endogenous metabolites in urine samples that come from pneumonia patients of6 months to 6 years old children were analyzed by metabolomics methods based on gas chromatography and mass spectrometry( GC-MS). The aim of this study was to analyze and study the pathogenesis of endogenous metabolites in children with pneumonia and the pathogenesis of pneumonia susceptibility. The urine samples were collected and divided into normal children group( NC group,n = 29),first infection with pneumonia group( FIP group,n = 35),and repeated infection with pneumonia group( RIP group,n = 31). The urine metabolic profile of pneumonia was obtained by GC-MS. Principal component analysis( PCA) and partial least squares-discriminant analysis( PLS-DA) were used to analyze the data. The results were analyzed by one-way analysis of variance and Fold change. Finally,there was significant difference between the normal group and the pneumonia group,the significant metabolites were serine,histidine,proline,norleucine,glutamine,stearic acid,valine,isoleucine with p value < 0. 05 and Fold change > 5,and indole-3-acetic acid,creatine,ethanolamine,mannosylglycerol and fructose were significant between the two pneumonia groups with p value<0.05. The urinary metabolites demonstrated that amino acid metabolism and glucose metabolism were the main metabolic pathways and responsible for the susceptibility to pneumonia.

关 键 词：小儿肺炎 易感性 代谢组学 气相色谱-质谱联用 

分 类 号：R725.6[医药卫生—儿科]