Abstract: Objective To analyze the composition and differences of important metabolites/products in premature infants without retinopathy of prematurity(non-ROP) and premature infants with retinopathy of prematurity(ROP), in order to find biomarkers closely related to the development of ROP. Methods Totally 21 premature infants with gestational age of 27~34 weeks and diagnosed with ROP in the Sixth Affiliated Hospital of Sun Yat-Sen University were enrolled as experimental group, and 21 premature infants without ROP were selected as control group from January 2013 to December 2016. Urine samples of the participants were collected and the Gas Chromatography-Mass Spectometry (GC/MS)was used to generate the urine metabolites results.Data collected were subjected to the metabolomics analysis by using the orthogonal partial least squares discriminant analysis to search for the considerable biomarkers. Results The urine metabolites from the ROP group and the non-ROP group displayed a clearly differentiated metabolic profiles.Ten metabolites were identified which possessed the biggest weight discriminating the ROP group from the non-ROP group in the pattern of recognizing process combined with the metabolites score plot with variable importance plot. ROP group had lower levels of methionine,3-amino-isobutyric acid and hippuric acid,while the level of 3-hydroxy-3-methylglutaric acid were significantly higher in the ROP group (all P＜0.05). Conclusion Urine metabolites including methionine,3-amino-isobutyric acid, hippuric acid and 3-hydroxy-3-methylglutaric acid can be selected as the biological markers for the early diagnosis of ROP.

Key words: gas chromatography-mass spectrometry, retinopathy of prematurity, premature infant, urine metabolites

摘要： 目的 探讨早产儿视网膜病(ROP)患儿出生尿代谢产物特征性变化,以期为ROP的诊断提供新的生物标记物。方法 收集2013年1月—2016年12月于中山大学附属第六医院住院的21例ROP实验组患儿及同期21例非ROP对照组患儿尿液标本,利用气相色谱-质谱技术进行代谢产物测定,运用正交偏最小二乘判别分析法(OPLS-DA)进行代谢组学分析。结果 联合代谢聚类图与权重图分析发现10个权重较大的物质(油酸、犬尿酸、2-甲基3-羟基丁酸、3-氨基异丁酸、3-羟基3-甲基戊二酸、马尿酸、蛋氨酸、甘油酸、次黄嘌呤和4-羟基苯乳酸)中ROP组患儿尿甲硫氨酸、3-氨基异丁酸、马尿酸水平明显降低,3-羟基3-甲基戊二酸明显升高,与对照组比较差异均具有统计学意义(P均<0.05)。结论 尿甲硫氨酸、3-羟基-3-甲基戊二酸、3-氨基异丁酸、马尿酸等代谢产物在ROP早期诊断中具有潜在的应用价值。

关键词: 气相色谱-质谱, 早产儿视网膜病变, 早产儿, 尿代谢产物