中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (4): 1042-1057.doi: 10.4103/NRR.NRR-D-23-01604

• 综述:脊髓损伤修复保护与再生 • 上一篇    下一篇

代谢重编程:治疗脊髓损伤的新选择

  

  • 出版日期:2025-04-15 发布日期:2024-06-30
  • 基金资助:
    国家自然科学基金(82202681),浙江省自然科学基金(LZ22H090003、LR23H060001)

Metabolic reprogramming: a new option for the treatment of spinal cord injury

Jiangjie Chen1, 2, 3, 4, #, Jinyang Chen1, 2, 3, 4, #, Chao Yu1, 2, 3, 4, Kaishun Xia1, 2, 3, 4, Biao Yang5 , Ronghao Wang1, 2, 3, 4, Yi Li1, 2, 3, 4, Kesi Shi1, 2, 3, 4, Yuang Zhang1, 2, 3, 4, Haibin Xu1, 2, 3, 4, Xuesong Zhang6 , Jingkai Wang1, 2, 3, 4, *, Qixin Chen1, 2, 3, 4, *, Chengzhen Liang1, 2, 3, 4, *   

  1. 1 Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; 2 Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, Zhejiang Province, China; 3 Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, Zhejiang Province, China; 4 Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, Zhejiang Province, China; 5 Qiandongnan Prefecture People’s Hospital, Kaili, Guizhou Province, China; 6 Department of Orthopedics, Fourth Medical Center, Chinese PLA General Hospital, Beijing, China
  • Online:2025-04-15 Published:2024-06-30
  • Contact: Chengzhen Liang, PhD, liangchengzhen@zju.edu.cn; Qixin Chen, MD, zrcqx@zju.edu.cn; Jingkai Wang, PhD, kingjay@zju.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82202681 (to JW) and the Natural Science Foundation of Zhejiang Province, Nos. LZ22H090003 (to QC), LR23H060001 (to CL).

摘要:

脊髓损伤由于其严重的后遗症,给社会带来了巨大的经济负担。目前针对脊髓损伤的许多治疗方法仍在研发中,但效果均不理想。随着对代谢研究的深入理解,在脊髓损伤发生前后神经代谢格局的改变为治疗脊髓损伤的提供了新的见解。该综述讨论了脊髓损伤期间的代谢变化、由此产生的后果以及用于代谢重编程的可用的治疗工具。正常的脊髓代谢包括独立的细胞代谢和细胞间代谢耦合。随后,文章介绍了与脊髓损伤相关的代谢紊乱,包括葡萄糖代谢紊乱、脂质代谢紊乱和线粒体功能障碍。这些代谢紊乱导致了相应的病理变化,包括轴突再生失败、瘢痕积累和微胶质细胞的活化。为了在代谢水平上挽救脊髓损伤,目前已经研究出了可改变细胞命运的代谢重编程策略,包括补充代谢底物、重建代谢耦合和针对线粒体的治疗等。上述证据表明,代谢重编程有望成为治疗脊髓损伤的下一代方法。未来脊髓代谢治疗的重点将是深入了解神经代谢、更好地开发代谢组学技术以及设计高效的代谢干预措施。

https://orcid.org/0000-0002-2948-2141 (Chengzhen Liang); https://orcid.org/0000-0002-2626-0201 (Qixin Chen); https://orcid.org/0000-0002-2626-0201 (Jingkai Wang)

关键词: 脊髓损伤, 代谢, 神经再生, 代谢重编程, 糖酵解, 氧化磷酸化, 线粒体, 轴突, 治疗, 神经保护

Abstract: Spinal cord injuries impose a notably economic burden on society, mainly because of the severe after-effects they cause. Despite the ongoing development of various therapies for spinal cord injuries, their effectiveness remains unsatisfactory. However, a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming. In this review, we explore the metabolic changes that occur during spinal cord injuries, their consequences, and the therapeutic tools available for metabolic reprogramming. Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling. However, spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism, lipid metabolism, and mitochondrial dysfunction. These metabolic disturbances lead to corresponding pathological changes, including the failure of axonal regeneration, the accumulation of scarring, and the activation of microglia. To rescue spinal cord injury at the metabolic level, potential metabolic reprogramming approaches have emerged, including replenishing metabolic substrates, reconstituting metabolic couplings, and targeting mitochondrial therapies to alter cell fate. The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury. To further advance the metabolic treatment of the spinal cord injury, future efforts should focus on a deeper understanding of neurometabolism, the development of more advanced metabolomics technologies, and the design of highly effective metabolic interventions.

Key words: axons, glycolysis, metabolic reprogramming, metabolism, mitochondria, neural regeneration, neuroprotection, oxidative phosphorylation, spinal cord injury, therapy