中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (6): 959-968.doi: 10.4103/1673-5374.208591

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

去铁胺促进脊髓挫伤后功能恢复的作用途径

  

  • 收稿日期:2017-05-22 出版日期:2017-06-15 发布日期:2017-06-15
  • 基金资助:

    国家自然科学基金（81672171, 81330042, 81620108018）；中国科技部技术基金（2014dfr31210）；天津科学技术委员会项目（13rcgfsy19000，14zczdsy00044），天津医科大学总医院青年基金（zyyfy2015008）

Mechanisms underlying the promotion of functional recovery by deferoxamine after spinal cord injury in rats

Jian Hao1, Bo Li1, Hui-quan Duan1, Chen-xi Zhao1, Yan Zhang1, Chao Sun1, Bin Pan1, Chang Liu2, Xiao-hong Kong2, Xue Yao1, 3, Shi-qing Feng1, 3   

  1. 1 Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China; 2 School of Medicine, Nankai University, Tianjin, China; 3 Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
  • Received:2017-05-22 Online:2017-06-15 Published:2017-06-15
  • Contact: Xue Yao, Ph.D. or Shi-qing Feng, M.D., xueyao@tmu.edu.cn or sqfeng@tmu.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81672171, 81330042; the International Cooperation Program of National Natural Science Foundation of China, No. 81620108018; a grant from the Ministry of Science and Technology of China, No. 2014DFR31210; a grant from the Tianjin Science and Technology Committee of China, No. 13RCGFSY19000, 14ZCZDSY00044; the Youth Foundation of Tianjin Medical University General Hospital of China, No. ZYYFY2015008.

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摘要：

 

去铁胺(DFO)是一种临床上治疗铁离子过载疾病的药物，有报道称其可用于修复脊髓损伤，但是具体机制不详。实验设计采用脊髓损伤打击器制作脊髓胸10(T10)节段脊髓挫伤大鼠模型，采用去铁胺腹腔注射，设Injury+DFO组，Injury组作对照。结果显示，脊髓损伤后2 days，2 weeks，和Injury相比，Injury+DFO组大鼠脊髓组织总铁离子水平、促炎因子肿瘤坏死因子α、白细胞介素1β、促凋亡蛋白Caspase-3蛋白表达、星型胶质细胞标志物GFAP免疫阳性面积、TUNEL阳性细胞数量明显降低，神经元标记物NeuN免疫阳性细胞数量及少突胶质细胞标志物CNPase阳性面积增加。脊髓损伤后14-56 d，损伤+DFO组大鼠后肢运动功能优于损伤组。结果说明，DFO可降低脊髓损伤后总铁离子水平、肿瘤坏死因子α和白细胞介素1β蛋白的表达，并且抑制细胞凋亡和胶质瘢痕形成，促进运动功能恢复。

ORCID:0000-0001-9437-7674(Shi-qing Feng)；0000-0003-4904-7697(Xue Yao)

关键词: 神经再生, 脊髓损伤, 去铁胺, 肿瘤坏死因子&alpha, 白细胞介素1&beta, 凋亡, 铁, 胶质瘢痕, 抗炎, 促炎, 胶质瘢痕, 大鼠, 运动功能, 脂质过氧化

Abstract:

Deferoxamine, a clinically safe drug used for treating iron overload, also repairs spinal cord injury although the mechanism for this action remains unknown. Here, we determined whether deferoxamine was therapeutic in a rat model of spinal cord injury and explored potential mechanisms for this effect. Spinal cord injury was induced by impacting the spinal cord at the thoracic T10 vertebra level. One group of injured rats received deferoxamine, a second injured group received saline, and a third group was sham operated. Both 2 days and 2 weeks after spinal cord injury, total iron ion levels and protein expression levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β and the pro-apoptotic protein caspase-3 in the spinal cords of the injured deferoxamine-treated rats were significantly lower than those in the injured saline-treated group. The percentage of the area positive for glial fibrillary acidic protein immunoreactivity and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were also significantly decreased both 2 days and 2 weeks post injury, while the number of NeuN-positive cells and the percentage of the area positive for the oligodendrocyte marker CNPase were increased in the injured deferoxamine-treated rats. At 14–56 days post injury, hind limb motor function in the deferoxamine-treated rats was superior to that in the saline-treated rats. These results suggest that deferoxamine decreases total iron ion, tumor necrosis factor-α, interleukin-1β, and caspase-3 expression levels after spinal cord injury and inhibits apoptosis and glial scar formation to promote motor function recovery.

Key words: nerve regeneration, spinal cord injury, deferoxamine, tumor necrosis factor-α, interleukin-1β, apoptosis, iron, anti-inflammatory, glial scar, proinflammatory, rats, motor function, lipid peroxidation, neural regeneration