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脑性瘫痪患儿暴露于肉毒神经毒素后的血浆代谢组学变化。

Plasma Metabolomic Changes in Children with Cerebral Palsy Exposed to Botulinum Neurotoxin.

机构信息

Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510120, Guangzhou China.

Department of Rehabilitation, School of Medicine, South China University of Technology, Guangzhou 510655, China.

出版信息

J Proteome Res. 2022 Mar 4;21(3):671-682. doi: 10.1021/acs.jproteome.1c00711. Epub 2022 Jan 12.

Abstract

The long-term effect of botulinum neurotoxin A (BoNT-A) on children with cerebral palsy (CP) is unclear, and how the dynamic changes of metabolites impact the duration of effect remains unknown. To tackle this, we collected 120 plasma samples from 91 children with spastic CP for analysis, with 30 samples in each time point: prior to injection and 1, 3, and 6 months after injection. A total of 354 metabolites were identified across all the time points, 39 of which exhibited significant changes (with tentative IDs) ( values <0.05, VIP > 1). Principal component analysis and partial least-squares discriminant analysis disclosed a clear separation between different groups ( values <0.05). Network analysis revealed the coordinated changes of functional metabolites. Pathway analysis highlighted the metabolic pathways associated with energy consumption and glycine, serine, and threonine metabolism and cysteine and methionine metabolism. Collectively, our results identified the significant dynamic changes of plasma metabolite after BoNT-A injections on children with CP. Metabolic pathways associated with energy expenditure might provide a new perspective for the effect of BoNT-A in children with CP. Glycine, serine, and threonine metabolism and cysteine and methionine metabolism might be related to the duration of effect of BoNT-A.

摘要

肉毒毒素 A(BoNT-A)对脑瘫(CP)患儿的长期疗效尚不清楚,代谢物的动态变化如何影响疗效持续时间尚不清楚。为了解决这个问题,我们收集了 91 例痉挛型 CP 患儿的 120 份血浆样本进行分析,每个时间点 30 份样本:注射前和注射后 1、3 和 6 个月。在所有时间点共鉴定出 354 种代谢物,其中 39 种(具有暂定 ID)表现出显著变化( values <0.05,VIP > 1)。主成分分析和偏最小二乘判别分析显示不同组之间有明显的分离( values <0.05)。网络分析揭示了功能代谢物的协调变化。途径分析突出了与能量消耗以及甘氨酸、丝氨酸和苏氨酸代谢和半胱氨酸和蛋氨酸代谢相关的代谢途径。总之,我们的研究结果确定了 BoNT-A 注射后 CP 患儿血浆代谢物的显著动态变化。与能量消耗相关的代谢途径可能为 BoNT-A 在 CP 患儿中的作用提供新的视角。甘氨酸、丝氨酸和苏氨酸代谢以及半胱氨酸和蛋氨酸代谢可能与 BoNT-A 的疗效持续时间有关。

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