选择性胎儿宫内生长受限与代谢异常的关系——基于气相色谱-飞行时间质谱的脐血代谢组学研究

Study on the relationship between selective intrauterine growth restriction(sIUGR) and metabolic disorder-Metabonomics Study of cord blood based on gas chromatography time-of-flight mass spectrometry(GC-TOF/MS)

目的探讨单绒毛膜双羊膜囊双胎选择性宫内生长受限(sIUGR)的脐血代谢物构成及生长受限胎儿与正常胎儿的代谢差异。方法采用单卵双胎配对设计,通过气相色谱-飞行时间质谱进行sIUGR双胎脐血代谢组学检测,采用主成分分析和偏最小二乘法判别分析(PLS-DA)对质谱数据建模,对变量投影重要度(VIP)值>1的差异点进行非参数检验,寻找差异代谢物。结果 sIUGR大小胎儿脐血血浆样品点在PLS-DA得分图中存在分离趋势。通过对VIP值大于1的差异点进行Wilcoxon符号秩检验及数据库比对,筛选出10种体现出大小胎儿代谢差别的脐血潜在标志物,在生长受限胎儿脐血代谢水平上调的代谢物包括山梨醇、肌醇、甘氨酸、吡啶甲酸,下调的包括亮氨酸、缬氨酸、棕榈酸、硬脂酸、胆固醇和肌酸。结论 sIUGR生长受限胎儿与正常胎儿的脐血代谢物构成存在差异,可能与碳水化合物、氨基酸及脂代谢异常相关。

Objective To investigate metabolite profiles of human umbilical cord blood in monochorionic diamnionic twin in selective intrauterine growth restriction （sIUGR） and the difference between IUGR and AGA.Methods Based on paired design,cord blood samples from sIUGR were detected by gas chromatography/time-of-flight mass spectrometry （GC-TOF/MS）.Principal component analysis （PCA） and partial least squares discrimination analysis （PLS-DA） were used for data modeling.Nonparametric tests were used to test variable importance in the projection （VIP） values which exceeding 1.0 as changed metabolites.Results IUGR group and the control group were distinguished from each other in PLS-DA score plot,10 different plasma metabolites were identified with the combination of VIP and Wilcoxon signed-rank test：sorbitol,creatine,glycine,picolinic acid were significantly increased in IUGR,while leucine,valine,palmitic acid,stearic acid,cholesterol and myo-inositol were significantly decreased （P-value 〈 0.05）.Conclusion There were differences in the composition of umbilical cord blood metabolites between sIUGR growth restricted fetus and normal fetus,which may be related to carbohydrate,amino acids and lipid metabolism abnormalities.