Chen Zhaofang, Peng Tingting, Zhong Mengru, Zhang Yage, Zhang Yuan, Hou Qingfen, Peng Tingting, Yang Xubo, Zhou Hongyu, Liu Liru, Han Mingshan, Tang Hongmei, He Lu, Li Jinling, Niu Huiran, Xu Kaishou
Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangzhou, China.
Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, Shanghai, China.
Pediatr Res. 2025 Apr 17. doi: 10.1038/s41390-025-04038-5.
We previously examined plasma metabolic changes before and after botulinum toxin-A injections of cerebral palsy (CP) children and showed that the glycine, serine and threonine metabolism may play a key role in neuritogenesis. This study analysed untargeted metabolomics combined with proteomics of plasma to discussed which substances are meaningfully changed, to what extent they affect the effects of action.
Blood samples were collected from 91 children with spastic CP at 4 time points: pre-injection (T1), 1 month post-injection (T2), 3 months post-injection (T3) and 6 months post-injection (T4). Differentially changed metabolites and proteins were selected, and co-expression pathways were constructed to explore the key molecular processes.
A total of 674 proteins and 354 metabolites were identified. The differential metabolites were mainly involved in the linoleic acid metabolism, beta-Alanine metabolism, citrate cycle, pyruvate metabolism and glycolysis or gluconeogenesis. Differential proteins were primarily associated with glucose metabolism, lipid metabolism, immune and inflammation responses. Co-expression pathways showed that ECM-receptor interaction, complement and coagulation cascades, glycolysis or gluconeogenesis, pyruvate metabolism, and linoleic acid metabolism were the main pathways.
Our results indicated the botulinum toxin-A predominantly activated the glucose metabolism, lipid metabolism, and immune and inflammation responses, and energy metabolism changed significantly in this process.
ChiCTR2000033800, Research on the mechanism of botulinum toxin relieving spasticity in children with cerebral palsy. Approval No. 202023041. Registered 13 June 2020, http://www.chictr.org.cn/showproj.html?proj=52267 .
This is the first study that combined dynamic metabolomics and proteomics analysis to investigate the molecular changes in children with spastic cerebral palsy after botulinum toxin-A injections, which might provide a theoretical reference for the further subsequent study for targets to increase the efficacy and prolong the duration of botulinum toxin-A, and would be a valuable resource for the metabolomics and proteomics field in this group.
我们之前研究了脑性瘫痪（CP）患儿注射A型肉毒毒素前后的血浆代谢变化，结果显示甘氨酸、丝氨酸和苏氨酸代谢可能在神经突形成中起关键作用。本研究分析了血浆的非靶向代谢组学并结合蛋白质组学，以探讨哪些物质发生了有意义的变化，以及它们对作用效果的影响程度。
采集91例痉挛型CP患儿在4个时间点的血样：注射前（T1）、注射后1个月（T2）、注射后3个月（T3）和注射后6个月（T4）。筛选出差异变化的代谢物和蛋白质，并构建共表达通路以探索关键分子过程。
共鉴定出674种蛋白质和354种代谢物。差异代谢物主要参与亚油酸代谢、β-丙氨酸代谢、柠檬酸循环、丙酮酸代谢和糖酵解或糖异生。差异蛋白质主要与葡萄糖代谢、脂质代谢、免疫和炎症反应相关。共表达通路显示，细胞外基质-受体相互作用、补体和凝血级联反应、糖酵解或糖异生、丙酮酸代谢和亚油酸代谢是主要通路。
我们的结果表明，A型肉毒毒素主要激活了葡萄糖代谢、脂质代谢以及免疫和炎症反应，并且在此过程中能量代谢发生了显著变化。
ChiCTR2000033800，A型肉毒毒素缓解脑性瘫痪患儿痉挛机制的研究。批准文号202023041。于2020年6月13日注册，http://www.chictr.org.cn/showproj.html?proj=52267 。
这是第一项结合动态代谢组学和蛋白质组学分析来研究痉挛型脑性瘫痪患儿注射A型肉毒毒素后分子变化的研究，这可能为进一步后续研究提高A型肉毒毒素疗效和延长其作用持续时间的靶点提供理论参考，并且将成为该组代谢组学和蛋白质组学领域的宝贵资源。
