中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (6): 1054-1060.doi: 10.4103/1673-5374.233449

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

骨形态发生蛋白7局部注射可促进急性脊髓损伤后神经元再生及运动功能恢复

  

  • 收稿日期:2018-04-25 出版日期:2018-06-15 发布日期:2018-06-15
  • 基金资助:

    新疆生产建设兵团博士基金资助（2014B020）

Local injection of bone morphogenetic protein 7 promotes neuronal regeneration and motor function recovery after acute spinal cord injury

Chen Chen, Guang-Chao Bai, Hong-Liang Jin, Kun Lei, Kuan-Xin Li   

  1. Department of Joint and Spine, Xinjiang Production and Construction Corps Hospital, Urumqi, Xinjiang Uygur Autonomous Region, China
  • Received:2018-04-25 Online:2018-06-15 Published:2018-06-15
  • Contact: Kuan-Xin Li, Ph.D.,1483066519@qq.com.
  • Supported by:

    This study was supported by the Xinjiang Production and Construction Corps Doctoral Fund of China, No. 2014BB020.

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摘要：

有研究发现脊髓损伤后骨形态发生蛋白7阳性表达的胶质细胞增多，运动神经元中骨形态发生蛋白7蛋白的表达量也显增加，这可能预示脊髓损伤后骨形态发生蛋白7表达上调可能会促进神经修复。鉴于此，我们设想将骨形态发生蛋白7直接注射到大鼠损伤脊髓组织处，观察骨形态发生蛋白7蛋白对急性脊髓损伤大鼠神经功能恢复的影响。采用Allences′s 打击器造成大鼠T10脊髓损伤建立急性脊髓损伤大鼠模型，造模成功后每天对损伤处分别注射生理盐水和50 ng 骨形态发生蛋白7蛋白，连续7 d，设为模型组和骨形态发生蛋白7组。神经电生理检测可见，模型组及骨形态发生蛋白7组大鼠术后1周运动诱发电位(motor evoked potential, MEP)中N1波低于正常的N1波形，术后8周MEP波形多呈M形的双峰波，波幅较术后1周时明显升高，且骨形态发生蛋白7组的MEP波幅均高于模型组。BBB评分、苏木精-伊红染色及Western Blot显示，术后1，2，4，8周，与模型组相比，骨形态发生蛋白7组大鼠后肢BBB评分增加，脊髓损伤处尼尼氏体染色加深，尼氏体数量增多，空泡数量逐渐减少，神经突触数量增多，脊髓损伤节段神经元标记物神经丝蛋白（neurofilament protein 200, NF200）表达增加。Western Blot结果还显示，模型组及骨形态发生蛋白7组大鼠脊髓损伤节段星形胶质细胞标记物胶质纤维酸性蛋白（glial fibrillary acidic protein, GFAP）表达均在术后第2周时达到高峰，随后降低，两组间GFAP蛋白表达差异不显著。上述数据证实，骨形态发生蛋白7局部注射可促进大鼠急性脊髓损伤后神经元再生，并促进肢体运动功能恢复。

orcid:0000-0001-6319-1260(Kuan-Xin Li)

关键词: 骨形态发生蛋白7, 脊髓损伤, 行为学, BBB评分, 运动功能, MEP波, 尼氏体染色, 神经丝蛋白200, 胶质纤维酸性蛋白, 大鼠, 神经再生

Abstract:

After spinal cord injury, the number of glial cells and motor neurons expressing bone morphogenetic protein 7 (BMP7) increases, indicating that upregulation of BMP7 can promote nerve repair. We, therefore, tested whether direct injection of BMP7 into acutely injured rat spinal cord can affect neurological recovery. Allen’s impactor was used to create spinal cord injury at T10. The injury site was then injected with 50 ng BMP7 (BMP7 group) or physiological saline (control group) for 7 consecutive days. Electrophysiological examination showed that the amplitude of N1 in motor evoked potentials (MEP) decreased after spinal cord injury. At 8 weeks post-operation, the amplitude of N1 in the BMP7 group was remarkably higher than that at 1 week post-operation and was higher than that of the control group. Basso, Beattie,Bresnahan scale (BBB) scores, hematoxylin-eosin staining, and western blot assay showed that at 1, 2, 4 and 8 weeks post-operation,BBB scores were increased; Nissl body staining was stronger; the number of Nissl-stained bodies was increased; the number of vacuoles gradually decreased; the number of synapses was increased; and the expression of neuronal marker, neurofilament protein 200, was increased in the hind limbs of the BMP7 group compared with the control group. Western blot assay showed that the expression of GFAP protein in BMP7 group and control group did not change significantly and there was no significant difference between the BMP7 and control groups. These data confirmed that local injection of BMP7 can promote neuronal regeneration after spinal cord injury and promote recovery of motor function in rats.

Key words: nerve regeneration, behavior, Basso, Beattie, Bresnahan scale score, motor evoked potential wave, Nissl staining, neurons, glial cells, neurofilament protein 200, glial fibrillary acidic protein, neural regeneration