中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (8): 3677-3686.doi: 10.4103/NRR.NRR-D-24-00154

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

达夫奈肽促进损伤脊髓损伤结构和功能恢复的自噬机制

  

  • 出版日期:2026-08-18 发布日期:2026-04-27

Davunetide promotes structural and functional recovery of the injured spinal cord by promoting autophagy#br#

Yituo Chen1, 2, 3, #, Rongjie Liu1, 2, 3, #, Wanta Cai1, 2, 3, Liting Jiang1, 2, 3, Kongbin Chen1, 2, 3, Jingwei Shi4, Junsheng Lou5, Letian Yu6, Chenyu Wu1, 2, 3, Liangliang Yang4, 7, *, Kailiang Zhou1, 2, 3, *, Wenfei Ni1, 2, 3, *   

  1. 1Department of Orthopedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; 
    2Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China; 
    3The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; 
    4Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, Zhejiang Province, China; 
    5Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; 
    6Renji College of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; 
    7School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Provine, China
  • Online:2026-08-18 Published:2026-04-27
  • Contact: Liangliang Yang, MD, PhD, liangliangyangLLL@126.com; Kailiang Zhou, MD, PhD, zhoukailiang@wmu.edu.cn; Wenfei Ni, MD, PhD, niwenfei@126.com.
  • Supported by:
    This study was supported by the Natural Science Foundation of Zhejiang Province, No. LY21H060009 (to WN); National Natural Science Foundation of China, Nos. 82072192 and 82372540 (to KZ); Medical and Health Technology Plan Project of Zhejiang Province, No. 2024KY155 (to KZ); Natural Science Foundation of Ningbo, No. 2023J256 (to KZ); Science and Technology Bureau Foundation of Wenzhou, No. Y20220211 (to CW).

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摘要：

脊髓损伤后，细胞程序性死亡是一种常见现象。在这种情况下，自噬在清除细胞碎片方面起着至关重要的作用，而坏死则会扩大神经炎症并进一步破坏神经结构。神经保护药物达夫奈肽在治疗脑部疾病方面效果显著，但其在脊髓损伤中的作用尚不清楚，因此实验主要集中在其对脊髓损伤后细胞死亡调控的影响上。实验建立了脊髓挫伤小鼠模型，以每天0.5 µg/5µL 的剂量鼻内注射达夫奈肽。实验通过足迹分析和 BMS 评分对小鼠运动功能进行评估，同时使用 Masson 三色染色法评估脊髓损伤损伤程度。通过 Western 印迹和免疫荧光染色检测了与这一过程相关的蛋白表达，并使用免疫沉淀技术研究了蛋白之间的相互作用。实验结果显示，达夫奈肽不仅能缩小脊髓损伤小鼠的脊髓损伤面积，还能促进其运动功能的恢复。具体而言，达夫奈肽通过促进自噬和抑制坏死性凋亡来发挥作用，且抑制自噬会抵消脊髓损伤对坏死性凋亡的抑制效果。进一步的机制研究表明，达夫奈肽通过SIRT1-FOXO1-TFEB信号通路发挥作用，这一通路在达夫奈肽的治疗效果中起着关键作用。这项研究的意义在于揭示了达夫奈肽在脊髓损伤治疗中的潜在作用和机制，为开发新的脊髓损伤治疗策略提供了科学依据。


https://orcid.org/0000-0001-7795-576X (Kailiang Zhou); https://orcid.org/0000-0002-5344-1497 (Wenfei Ni)

关键词: 自噬, 达夫奈肽, 运动功能恢复, NAP, 坏死, 神经元, Sirtuin1, 脊髓损伤, 转录因子 EB

Abstract: After spinal cord injury, programmed cell death is common. In this context, autophagy plays a crucial role in clearing cellular debris, while necroptosis exacerbates neuroinflammation and further damages neural structures. The neuroprotective drug davunetide has shown substantial therapeutic effects on brain diseases, but its role in treating spinal cord injury remains unclear. Therefore, the aim of this study was to investigate the effects of davunetide on cell death after spinal cord injury. To do this, we established a mouse model of spinal cord contusion and administered davunetide intranasally daily at a dose of 0.5 µg/5 µL. Mouse locomotor function was assessed using footprint analysis and Basso Mouse Scale scoring, while the extent of spinal cord injury was evaluated using Masson’s trichrome staining. The expression levels of proteins related to locomotor function and spinal cord injury were analyzed by Western blotting and immunofluorescence staining, and protein–protein interactions were evaluated using immunoprecipitation techniques. Our results demonstrated that davunetide not only reduced the size of the injury area but also promoted the recovery of locomotor function after spinal cord injury. Specifically, davunetide exerted its effects by enhancing autophagy and inhibiting necroptosis. Inhibition of autophagy reversed the protective effects of davunetide on necroptosis. Further investigation revealed that davunetide acted through the SIRT1-FOXO1-TFEB signaling pathway, which is key to its therapeutic effects. These findings suggest the potential of davunetide in the treatment of spinal cord injury and provide valuable insights into the underlying mechanisms. This study offers strong scientific evidence to support the development of new therapeutic strategies for spinal cord injury.

Key words: autophagy, davunetide, locomotor function recovery, NAP, necroptosis, neuron, Sirtuin1, spinal cord injury, transcription factor EB