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基于高效液相色谱-(四极杆)-飞行时间质谱联用技术,利用动物模型对儿科人群中与年龄相关的血浆代谢谱差异进行的研究。

HPLC-(Q)-TOF-MS-Based Study of Plasma Metabolic Profile Differences Associated with Age in Pediatric Population Using an Animal Model.

作者信息

Albóniga Oihane E, González-Mendia Oskar, Blanco María E, Alonso Rosa M

机构信息

Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain.

Metabolomics Platform, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, 48160 Bilbao, Spain.

出版信息

Metabolites. 2022 Aug 11;12(8):739. doi: 10.3390/metabo12080739.

Abstract

A deep knowledge about the biological development of children is essential for appropriate drug administration and dosage in pediatrics. In this sense, the best approximation to study organ maturation is the analysis of tissue samples, but it requires invasive methods. For this reason, surrogate matrices should be explored. Among them, plasma emerges as a potential alternative since it represents a snapshot of global organ metabolism. In this work, plasma metabolic profiles from piglets of different ages (newborns, infants, and children) obtained by HPLC-(Q)-TOF-MS at positive and negative ionization modes were studied. Improved clustering within groups was achieved using multiblock principal component analysis compared to classical principal component analysis. Furthermore, the separation observed among groups was better resolved by using partial least squares-discriminant analysis, which was validated by bootstrapping and permutation testing. Thanks to univariate analysis, 13 metabolites in positive and 21 in negative ionization modes were found to be significant to discriminate the three groups of piglets. From these features, an acylcarnitine and eight glycerophospholipids were annotated and identified as metabolites of interest. The findings indicate that there is a relevant change with age in lipid metabolism in which lysophosphatidylcholines and lysophoshatidylethanolamines play an important role.

摘要

深入了解儿童的生物发育对于儿科合理用药和确定剂量至关重要。从这个意义上讲,研究器官成熟的最佳方法是分析组织样本,但这需要采用侵入性方法。因此,应探索替代基质。其中,血浆成为一种潜在的替代物,因为它代表了整体器官代谢的一个快照。在这项工作中,研究了通过HPLC-(Q)-TOF-MS在正离子和负离子模式下获得的不同年龄(新生儿、婴儿和儿童)仔猪的血浆代谢谱。与经典主成分分析相比,使用多块主成分分析实现了组内更好的聚类。此外,通过偏最小二乘判别分析,组间观察到的分离得到了更好的解析,并通过自举法和排列检验进行了验证。通过单变量分析,发现在正离子模式下有13种代谢物、在负离子模式下有21种代谢物对区分三组仔猪具有显著意义。从这些特征中,一种酰基肉碱和八种甘油磷脂被注释并鉴定为感兴趣的代谢物。研究结果表明,脂质代谢随年龄有相关变化,其中溶血磷脂酰胆碱和溶血磷脂酰乙醇胺起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21c/9413543/4e3439fd322a/metabolites-12-00739-g001.jpg

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