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帕金森病患者血清和纹状体代谢谱的变化——体外和体内 NMR 光谱研究。

Changes in the metabolic profiles of the serum and putamen in Parkinson's disease patients - In vitro and in vivo NMR spectroscopy studies.

机构信息

Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, 4 Ks. Trojdena st., 02-109 Warsaw, Poland.

Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego st., 02-109 Warsaw, Poland.

出版信息

Brain Res. 2020 Dec 1;1748:147118. doi: 10.1016/j.brainres.2020.147118. Epub 2020 Sep 12.

Abstract

The aim of this study was to investigate the relationship between serum metabolomic biomarkers and brain in vivo magnetic resonance spectroscopy (MRS) biomarkers in patients with Parkinson's disease (PD) as well as to investigate compound concentration changes by comparing the results with healthy control subjects. Univariate statistical analysis of the serum showed significant differences in the levels of phenylalanine, tyrosine, lysine, glutamine, glutamate, acetone, acetate, 3-hydroxybutyrate, and 1-monoacylglycerol (1-MAG) between the PD patient group and the control group. Orthogonal partial least squares discriminant analysis showed significantly different compound concentrations of acetate, 3-hydroxybutyrate, glutamine, tyrosine, 1-MAG and testosterone. In vivo MRS of the putamen showed significantly higher concentrations of glutamine/glutamate complex and glutamine in patients with PD in comparison to control subjects. Following disrupted metabolic pathways in patients with PD were identified: dopamine synthesis, steroid hormone biosynthesis, fatty acid biosynthesis, the synthesis and degradation of ketone bodies, the metabolism of pyruvate, arginine, proline, alanine, aspartate, glutamate, tyrosine and phenylalanine. The obtained results may indicate changes in neurotransmission, disturbances in energy production and an altered cell membrane structure.

摘要

本研究旨在探讨帕金森病(PD)患者血清代谢组学生物标志物与脑体内磁共振波谱(MRS)生物标志物之间的关系,并通过与健康对照组比较来研究化合物浓度的变化。血清的单变量统计分析显示,PD 患者组与对照组之间的苯丙氨酸、酪氨酸、赖氨酸、谷氨酰胺、谷氨酸、丙酮、乙酸、3-羟基丁酸和 1-单酰基甘油(1-MAG)水平存在显著差异。正交偏最小二乘判别分析显示,乙酸、3-羟基丁酸、谷氨酰胺、酪氨酸、1-MAG 和睾酮的化合物浓度存在显著差异。与对照组相比,PD 患者的壳核体内 MRS 显示出更高的谷氨酰胺/谷氨酸复合物和谷氨酰胺浓度。在 PD 患者中确定了以下代谢途径的紊乱:多巴胺合成、类固醇激素生物合成、脂肪酸合成、酮体的合成和降解、丙酮酸、精氨酸、脯氨酸、丙氨酸、天冬氨酸、谷氨酸、酪氨酸和苯丙氨酸的代谢。所得结果可能表明神经递质传递发生变化、能量产生紊乱和细胞膜结构改变。

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