中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (12): 2702-2709.doi: 10.4103/1673-5374.339491

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

亚硒酸钠抑制铁死亡促进脊髓损伤后的神经功能恢复

  

  • 出版日期:2022-12-15 发布日期:2022-05-05
  • 基金资助:
    国家自然科学基金项目(81870979);中国康复研究中心科研基金项目(2020-02);长沙市自然科学基金项目(kq2014285)

Sodium selenite promotes neurological function recovery after spinal cord injury by inhibiting ferroptosis

Yi-Xin Chen1, 2, 3, 4, 5, 6, Talifu Zuliyaer1, 2, 3, 4, 5, Bin Liu7, Shuang Guo1, 2, 3, 4, 5, De-Gang Yang1, 2, 3, 4, 5, Feng Gao1, 2, 3, 4, 5, *, Yan Yu2, 3, 5, Ming-Liang Yang1, 2, 3, 4, 5, Liang-Jie Du1, 2, 3, 4, 5, Jian-Jun Li1, 2, 3, 4, 5, *#br#   

  1. 1School of Rehabilitation Medicine, Capital Medical University, Beijing, China; 2China Rehabilitation Science Institute, Beijing, China; 3Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China; 4Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China; 5Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China; 6Department of Rehabilitation Medicine, Xiangya Hospital of Central South University, Changsha, Hunan Province, China; 7Department of Spine Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, China
  • Online:2022-12-15 Published:2022-05-05
  • Contact: Jian-Jun Li, 13718331416@163.com; Feng Gao, PhD, gaofeng5960@126.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81870979 (to JJL); the Scientific Research Foundation of China Rehabilitation Research Center, No. 2020-02 (to JJL); and the Natural Science Foundation of Changsha, No. kq2014285 (to YXC).

摘要:

硒已被证实可通过抑制铁死亡来促进脑出血后神经功能的恢复,但其硒是否也能促进脊髓损伤后的神经功能恢复以及作用机制仍有待阐明。实验在T10脊髓挫伤大鼠模型损伤后10min时,于损伤脊髓注射亚硒酸钠(3 µL,2.5 µM)。可见亚硒酸钠治疗能显著降低脊髓损伤大鼠脊髓组织中铁以及脂质过氧化产物丙二醛和4-羟基壬烯醛水平,促进特异性蛋白1和谷胱甘肽过氧化物酶4蛋白及mRNA的表达,促进神经元和少突胶质细胞的存活,抑制星形胶质细胞的增殖,进而促进运动功能的恢复。表明亚硒酸钠可改善脊髓损伤大鼠的运动功能,其作用可能是通过特异性蛋白1/谷胱甘肽过氧化物酶4通路抑制铁死亡实现的。

https://orcid.org/000-0003-2663-5971 (Jian-Jun Li); https://orcid.org/0000-0002-9525-8324 (Feng Gao)

关键词: 脊髓损伤, 铁死亡, 继发性损伤, 铁, 亚硒酸钠, 谷胱甘肽过氧化物酶4, 特异性蛋白, 谷胱甘肽, 脂质过氧化, 神经再生

Abstract: Ferroptosis is a recently discovered form of iron-dependent cell death, which occurs during the pathological process of various central nervous system diseases or injuries, including secondary spinal cord injury. Selenium has been shown to promote neurological function recovery after cerebral hemorrhage by inhibiting ferroptosis. However, whether selenium can promote neurological function recovery after spinal cord injury as well as the underlying mechanism remain poorly understood. In this study, we injected sodium selenite (3 µL, 2.5 µM) into the injury site of a rat model of T10 vertebral contusion injury 10 minutes after spinal cord injury modeling. We found that sodium selenite treatment greatly decreased iron concentration and levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal. Furthermore, sodium selenite increased the protein and mRNA expression of specificity protein 1 and glutathione peroxidase 4, promoted the survival of neurons and oligodendrocytes, inhibited the proliferation of astrocytes, and promoted the recovery of locomotive function of rats with spinal cord injury. These findings suggest that sodium selenite can improve the locomotive function of rats with spinal cord injury possibly through the inhibition of ferroptosis via the specificity protein 1/glutathione peroxidase 4 pathway. 

Key words: ferroptosis, glutathione peroxidase 4, glutathione, iron, lipid peroxidation, neural regeneration, secondary injury, sodium selenite, specificity protein 1, spinal cord injury