尿有机酸代谢异常与早产儿视网膜病变的相关性分析  

Correlation between abnormal urinary organic acid metabolism and retinopathy of prematurity

作　　者：何露 孙慧清[1] He Lu;Sun Huiqing(Department of Neonatology,Children's Hospital Affiliated to Zhengzhou University,Henan Children’s Hospital,Zhengzhou 450000,China)

机构地区：[1]郑州大学附属儿童医院河南省儿童医院新生儿科系,郑州450000

出　　处：《中华眼底病杂志》2024年第6期434-442,共9页Chinese Journal of Ocular Fundus Diseases

基　　金：河南省中青年卫生健康科技创新领军人才培养项目(YXKC2021022)。

摘　　要：目的观察早产儿视网膜病变(ROP)患儿尿代谢产物氨基酸水平变化及其对ROP的影响,初步分析其可能参与ROP发生的氨基酸代谢途径。方法回顾性队列研究。2020年1月至2023年12月于郑州大学附属儿童医院住院治疗且出生胎龄<32周的重度ROP患儿65例(ROP组)纳入研究。选取性别、孕周匹配且眼底无ROP的早产儿50名作为对照组。采用气相色谱质谱联用仪检测尿液中尿氨基酸及衍生物。两组比较采用独立样本t检验。采用正交偏最小二乘判别分析(OPLS-DA)模型对尿氨基酸进行代谢组学分析,变量投影重要性(VIP)分值>1提示该物质为两组差异表达氨基酸。采用受试者工作特征(ROC)曲线和曲线下面积比较尿氨基酸对重度ROP的预测价值。对t检验及代谢组学分析两组差异较大的氨基酸归一化后进行对比并行Pearson相关性分析。采用京都基因和基因组百科全书数据库富集分析差异表达氨基酸参与ROP发生的代谢通路。结果与对照组比较,ROP组患儿尿代谢产物中草酸-2、亚硫基二乙酸-2浓度明显降低,4-羟基丁酸-2、3-甲基戊烯二酸-2(1)、2-酮戊二酸-OX-2(2)、3,6-环氧-十二烷二酸-2浓度明显升高,差异有统计学意义(t=0.036、0.005、0.038、0.032、0.022、0.011,P<0.05)。OPLS-DA分析结果显示,ROP组、对照组受检儿尿代谢产物氨基酸分布于散点图的左右两个区域,两组之间呈现满意分离趋势(R2 Ycum=0.0574,Q2cum=0.0257,P<0.05);S-plot图显示偏向两极的氨基酸分别是乙醇酸-2、磷酸-3、草酸-2、亚硫基二乙酸-2、4-羟基丁酸-2、3-甲基巴豆酰甘氨酸-1、3-甲基戊烯二酸-2(1)、2-酮戊二酸-OX-2(2)、3,6-环氧-十二烷二酸-2;筛选出VIP分值>1的差异表达氨基酸11个,其中VIP分值最高的是草酸-2、甘油酸-3、磷酸-3、3-甲基巴豆酰甘氨酸-1、尿黑酸-3、亚硫基二乙酸-2。两组氨基酸浓度差异最大的为4-羟基丁酸-2和亚硫基二乙酸-2;草酸-2与Objective To investigate the postnatal changes in urinary metabolic amino acid levels in infants with retinopathy of prematurity(ROP)and their effect on ROP,and to analyze the amino acid metabolic pathways that may be involved in the development of ROP.Methods A retrospective cohort study.From January 2020 to December 2023,65 premature infants with severe ROP(ROP group)who were hospitalized,born with gestational age<32 weeks in Children's Hospital Affiliated to Zhengzhou University were included in the study.Fifty premature infants with matched sex and gestational age and no ROP were selected as the control group.Urine amino acids and their derivatives were detected by gas chromatography-mass spectrometry.The two groups were compared by independent sample t test.The metabonomics of urinary amino acids was analyzed by orthogonal partial least squares discriminant analysis(OPLS-DA)model.The variable projection importance(VIP)score>1 suggested that the substance was two groups of differentially expressed amino acids.The predictive value of urinary amino acids for severe ROP was compared by using the receiver's operating characteristic(ROC)curve and the area under the curve.After t test and metabolomics analysis,the two groups of amino acids with large differences were normalized and compared by Pearson correlation analysis.The Kyoto Encyclopedia of Genes and Genomes database was used to analyze the metabolic pathways of differentially expressed amino acids involved in ROP.Results Compared with the control group,the concentrations of oxalic acid-2 and thiodiacetic acid-2 in urine metabolites of children in ROP group were significantly decreased,while the concentrations of 4-hydroxybutyric acid-2,3-methylpentadienoic acid-2(1),2-ketoglutarate-ox-2(2)and 3,6-epoxy-dodecanedioic acid-2 were significantly increased,with statistical differences(t=0.036,0.005,0.038,0.032,0.022,0.011;P<0.05).The results of OPLS-DA analysis showed that amino acids of urinary metabolites in ROP group and control group were distributed in the

关 键 词：早产儿尿代谢 早产儿视网膜病变 尿氨基酸 尿代谢产物 

分 类 号：R722.6[医药卫生—儿科] R774.1[医药卫生—临床医学]