Wu Chenyu, Chen Yu, Chen Ximiao, Zhang Yekai, Zhao Xiaoying, Deng Yuxin, Li Chenchao, Zhang Di, Zhang Xiaolei, Wang Sheng
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang Province, Wenzhou, China.
Zhejiang Provincial Key Laboratory of Orthopedics, Zhejiang Province, Wenzhou, China.
Mol Neurobiol. 2025 Jan;62(1):445-460. doi: 10.1007/s12035-024-04283-5. Epub 2024 Jun 12.
Spinal cord injury (SCI) can lead to permanent paralysis and various motor, sensory and autonomic nervous system dysfunction. The complex pathophysiological processes limit the effectiveness of many clinical treatments. Mitochondria has been reported to play a key role in the pathogenesis of SCI; while mitophagy is a protective mechanism against mitochondrial dysfunction. However, there is recently little drugs that may targeted activate mitophagy to treat SCI. In this study, we evaluated the role of 20-Deoxyingenol (20-DOI) in SCI and explored its potential mechanisms. We used a SCI rat model and evaluated the functional outcomes after the injury. Western blotting and immunofluorescence techniques were used to analyze the levels of mitophagy, apoptosis, and TFEB-related signaling pathways. Our research results show that 20-DOI significantly improves the apoptosis of neural cells after TBHP stimulation and functional recovery after spinal cord injury. In addition, mitophagy, TFEB levels, and apoptosis are related to the mechanism of 20-DOI treatment for spinal cord injury. Specifically, our research results indicate that 20-DOI restored the autophagic flux after injury, thereby inducing mitophagy, eliminating the accumulation of Cyto C, and inhibiting apoptosis. Further mechanism research suggests that 20-DOI may regulate mitophagy by promoting TFEB nuclear translocation. These results indicate that 20-DOI can significantly promote recovery after spinal cord injury, which may be a promising treatment method for spinal cord injury.
脊髓损伤（SCI）可导致永久性瘫痪以及各种运动、感觉和自主神经系统功能障碍。复杂的病理生理过程限制了许多临床治疗的效果。据报道，线粒体在SCI的发病机制中起关键作用；而线粒体自噬是一种针对线粒体功能障碍的保护机制。然而，目前几乎没有可靶向激活线粒体自噬来治疗SCI的药物。在本研究中，我们评估了20-脱氧银杏酚（20-DOI）在SCI中的作用，并探讨了其潜在机制。我们使用了SCI大鼠模型并评估了损伤后的功能结局。采用蛋白质免疫印迹法和免疫荧光技术分析线粒体自噬、凋亡及与转录因子EB（TFEB）相关信号通路的水平。我们的研究结果表明，20-DOI可显著改善叔丁基过氧化氢（TBHP）刺激后神经细胞的凋亡以及脊髓损伤后的功能恢复。此外，线粒体自噬、TFEB水平和凋亡与20-DOI治疗脊髓损伤的机制有关。具体而言，我们的研究结果表明，20-DOI可恢复损伤后的自噬流，从而诱导线粒体自噬，消除细胞色素C的积累，并抑制凋亡。进一步的机制研究表明，20-DOI可能通过促进TFEB核转位来调节线粒体自噬。这些结果表明，20-DOI可显著促进脊髓损伤后的恢复，这可能是一种有前景的脊髓损伤治疗方法。
