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对接受多种油类脂质乳剂治疗的极低出生体重儿甘油磷脂代谢进行非靶向代谢组学分析。

Untargeted metabolomics analysis of glycerophospholipid metabolism in very low birth weight infants administered multiple oil lipid emulsions.

作者信息

Zeng Xiaoyan, Yu Tao, Xia Luping, Ruan Zhiqiang

机构信息

Department of Neonatology, Hangzhou Women's Hospital, Hangzhou, 310016, Zhejiang, China.

Department of Intensive Care Unit, Hangzhou Women's Hospital, Hangzhou, 310016, Zhejiang, China.

出版信息

BMC Pediatr. 2024 Dec 31;24(1):849. doi: 10.1186/s12887-024-05343-4.

Abstract

BACKGROUND

To compare the impact of two different lipid emulsions, specifically a soybean oil-based emulsion and a multiple oil emulsion (soybean oil, medium-chain triglycerides, olive oil, and fish oil, SMOF), on serum metabolites of very low birth weight (VLBW) infants using untargeted metabolomics analysis.

METHODS

A comparative study was conducted on 25 VLBW infants hospitalized in neonatal intensive care units (NICU) of Hangzhou Women's Hospital in 2023. The infants were divided into the SMOF group (13 cases) and the soybean oil group (12 cases) based on the type of lipid emulsion used during parenteral nutrition. Serum samples were collected at birth and 14 days later from both groups. An untargeted metabolomics analysis was conducted on serum samples using Ultra-high Performance Liquid Chromatography - Tandem Mass Spectrometry (UHPLC-MS/MS). Differential metabolites were identified using Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) modeling, with criteria of variable importance in the projection (VIP) > 1 and false discovery rate (FDR) < 0.05. Functional annotation of the top 30 differential metabolites, ranked by VIP value, was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Subsequently, enrichment and topological analyses were conducted with MetaboAnalyst software to identify key metabolic pathways. Finally, receiver operating characteristic (ROC) analysis was performed on metabolites associated with the identified key metabolic pathways.

RESULTS

The metabolomic analysis revealed that, in the OPLS-DA model, no significant metabolite differences were found in umbilical cord blood between the two groups. However, 84 differential metabolites were identified in the 14-day samples from the SMOF group compared to the soybean oil group. According to MetaboAnalyst analysis, glycerophospholipid metabolism emerged as the most significantly altered metabolic pathway following the administration of SMOF lipid emulsion. Additionally, ROC curve analysis confirmed a significant increase in LysoPC(20:5), PE(16:0/20:5), and PE-NMe(22:5/16:0) metabolites in the SMOF group.

CONCLUSION

The administration of SMOF lipid emulsion in VLBW infants resulted in significant modifications of serum metabolites compared to traditional soybean oil-based lipid emulsions. Notably, glycerophospholipid metabolism was identified as the most prominently altered metabolic pathway. Metabolites, including LysoPC(20:5), PE(16:0/20:5), and PE-NMe(22:5/16:0), emerged as potential biomarkers.

CLINICAL TRIAL NUMBER

Not applicable.

摘要

背景

采用非靶向代谢组学分析方法,比较两种不同的脂质乳剂,即大豆油基乳剂和多油乳剂(大豆油、中链甘油三酯、橄榄油和鱼油,SMOF)对极低出生体重(VLBW)婴儿血清代谢物的影响。

方法

对2023年在杭州市妇产科医院新生儿重症监护病房(NICU)住院的25例VLBW婴儿进行了一项对比研究。根据肠外营养期间使用的脂质乳剂类型,将婴儿分为SMOF组(13例)和大豆油组(12例)。在出生时和出生14天后从两组采集血清样本。使用超高效液相色谱-串联质谱(UHPLC-MS/MS)对血清样本进行非靶向代谢组学分析。使用正交偏最小二乘判别分析(OPLS-DA)模型鉴定差异代谢物,投影变量重要性(VIP)>1且错误发现率(FDR)<0.05为标准。使用京都基因与基因组百科全书(KEGG)数据库对按VIP值排名的前30种差异代谢物进行功能注释。随后,使用MetaboAnalyst软件进行富集和拓扑分析,以确定关键代谢途径。最后,对与确定的关键代谢途径相关的代谢物进行受试者操作特征(ROC)分析。

结果

代谢组学分析显示,在OPLS-DA模型中,两组脐带血中未发现显著的代谢物差异。然而,与大豆油组相比,在SMOF组14天样本中鉴定出84种差异代谢物。根据MetaboAnalyst分析,给予SMOF脂质乳剂后,甘油磷脂代谢是变化最显著的代谢途径。此外,ROC曲线分析证实SMOF组中溶血磷脂酰胆碱(20:5)、磷脂酰乙醇胺(16:0/20:5)和N-甲基磷脂酰乙醇胺(22:5/16:0)代谢物显著增加。

结论

与传统的大豆油基脂质乳剂相比,给VLBW婴儿使用SMOF脂质乳剂导致血清代谢物发生显著改变。值得注意的是,甘油磷脂代谢被确定为变化最显著的代谢途径。包括溶血磷脂酰胆碱(20:5)、磷脂酰乙醇胺(16:0/20:5)和N-甲基磷脂酰乙醇胺(22:5/16:0)在内 的代谢物成为潜在的生物标志物。

临床试验编号

不适用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac4a/11686898/e4751c7628af/12887_2024_5343_Fig1_HTML.jpg

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