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多发性硬化症早期改变的脑脊髓液疏水性和亲水性化合物浓度-代谢谱分析。

Altered Cerebrospinal Fluid Concentrations of Hydrophobic and Hydrophilic Compounds in Early Stages of Multiple Sclerosis-Metabolic Profile Analyses.

机构信息

Department of Neurology, Medical University of Warsaw, Zwirki i Wigury 61, 02-091, Warsaw, Poland.

Department of Anesthesiology, Medical University of Warsaw, Zwirki i Wigury 61, 02-091, Warsaw, Poland.

出版信息

J Mol Neurosci. 2019 Sep;69(1):94-105. doi: 10.1007/s12031-019-01336-6. Epub 2019 May 27.

Abstract

The lack of a single predictive or diagnostic test in multiple sclerosis (MS) remains a major obstacle in the patient's care. The aim of this study was to investigate metabolic profiles, especially lipids in cerebrospinal fluid (CSF) using H-NMR spectroscopy and metabolomics analysis to discriminate MS patient group from the control ones. In this study, 19 MS patients and 19 controls, without neurological problems, patients were enrolled. To obtain the CSF metabolic profiles, NMR spectroscopy was used. Hydrophilic and hydrophobic compounds were analyzed using univariate and multivariate supervised analysis orthogonal partial least square discriminant analysis (OPLS-DA). Targeted OPLS-DA analysis of 32 hydrophilic and 17 hydrophobic compounds obtained 9 hydrophilic metabolites and 8 lipid functional groups which had the highest contribution to patient's group separation. Lower concentrations of CSF hydrophilic and hydrophobic compounds were observed in MS patients as compared to control group. Acetone, choline, urea, 1,3-dimethylurate, creatinine, isoleucine, myo-inositol, leucine, and 3-OH butyrate; saturated and monounsaturated acyl groups of ω-9, ω-7, ω-6, ω-3, and fatty acid, triglycerides, 1,3-DG, 1-MG, and unassigned component signal at 3.33 ppm were the most important signal compounds in group separation. Analysis of metabolic profile of raw CSF and their lipid extract shows decreased levels of many compounds and led to the conclusion that MS patients could have a disturbance in many metabolic pathways perhaps leading to the decreased level of acetyl-CoA and/or inflammation. CSF metabolic profile analyses could be used as a fingerprint for early MS diagnosis.

摘要

多发性硬化症(MS)缺乏单一的预测或诊断测试仍然是患者护理中的主要障碍。本研究旨在使用 H-NMR 光谱和代谢组学分析来研究代谢谱,尤其是脑脊液(CSF)中的脂质,以将 MS 患者组与对照组区分开来。在这项研究中,招募了 19 名 MS 患者和 19 名无神经问题的对照组患者。为了获得 CSF 代谢谱,使用 NMR 光谱。使用单变量和多变量监督分析正交偏最小二乘判别分析(OPLS-DA)分析亲水性和疏水性化合物。对 32 种亲水性和 17 种疏水性化合物进行靶向 OPLS-DA 分析,得到 9 种亲水性代谢物和 8 种脂质功能基团,它们对患者组分离的贡献最大。与对照组相比,MS 患者的 CSF 亲水性和疏水性化合物浓度较低。与对照组相比,MS 患者的 CSF 中观察到较低浓度的丙酮、胆碱、尿素、1,3-二甲基尿酸、肌酐、异亮氨酸、肌醇、亮氨酸和 3-OH 丁酸;饱和和单不饱和酰基ω-9、ω-7、ω-6、ω-3 和脂肪酸、甘油三酯、1,3-DG、1-MG 和未分配组分信号在 3.33 ppm 处是组分离的最重要信号化合物。对原始 CSF 和其脂质提取物的代谢谱分析表明,许多化合物的水平降低,并得出结论,MS 患者可能在许多代谢途径中存在紊乱,这可能导致乙酰辅酶 A 和/或炎症水平降低。CSF 代谢谱分析可作为早期 MS 诊断的指纹。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87a9/6689291/47633171ad72/12031_2019_1336_Fig1_HTML.jpg

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