中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (7): 1159-1165.doi: 10.4103/1673-5374.160114

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

β-神经生长因子促进骨缺损修复中的神经发生和血管生成

  

  • 收稿日期:2015-06-23 出版日期:2015-07-24 发布日期:2015-07-24

Beta-nerve growth factor promotes neurogenesis and angiogenesis during the repair of bone defects

Wei-hui Chen 1, Chuan-qing Mao 2, Li-li Zhuo 1, Joo L. Ong 2   

  1. 1 Department of Oral Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian Province, China
    2 Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, TX, USA
  • Received:2015-06-23 Online:2015-07-24 Published:2015-07-24
  • Contact: Wei-hui Chen, Ph.D., dr_whchen@yahoo.com.
  • Supported by:

     This work was supported by the Fujian Foundation for Distinguished Young Scientists in China, No. Grant#2060203; the National Natural Science Foundation of China, No. 31070838.

摘要:

我们既往研究发现,骨缺损修复过程受神经和血管因素的调控。为此,本次实验设计了在充填胶原骨粉进行骨缺损修复过程中,局部应用β-神经生长因子,观察其对神经发生和血管生成的影响。实验构建了直径2.5mm的颅骨圆形缺损模型,充填胶原骨粉进行修复,右侧颅骨缺损部位注射10 μg β-神经生长因子,左侧对照侧颅骨缺损部位注射PBS连续7d。免疫组化染色和苏木精-伊红染色显示,与对照侧相比,注射β-神经生长因子侧损伤部位,7d时神经分化标志物β III-tubulin表达下降,神经元标志物NF160表达增加,14d时β III-tubulin和神经元标志物PGP9.5表达增加,28d时PGP9.5表达降低,血管生成促进因子血管内皮生长因子表达在损伤后7d时增加,而血管内皮生长因子受体2表达在损伤后14,21d时增加,28d时减少,但两侧骨缺损部位血管数量接近。实验结果说明局部应用β-神经生长因子可影响充填胶原骨粉进行骨缺损修复的神经发生,且显示了通过促进神经发生调控了血管的生成。

关键词: 神经再生, β-NGF, 胶原, 血管生成, PGP9.5, 血管内皮生长因子, βIII-微管蛋白

Abstract:

We previously showed that the repair of bone defects is regulated by neural and vascular signals. In the present study, we examined the effect of topically applied β-nerve growth factor (β-NGF) on neurogenesis and angiogenesis in critical-sized bone defects filled with collagen bone substitute. We created two symmetrical defects, 2.5 mm in diameter, on either side of the parietal bone of the skull, and filled them with bone substitute. Subcutaneously implanted osmotic pumps were used to infuse 10 μg β-NGF in PBS (β-NGF + PBS) into the right-hand side defect, and PBS into the left (control) defect, over the 7 days following surgery. Immunohistochemical staining and hematoxylin-eosin staining were carried out at 3, 7, 14, 21 and 28 days postoperatively. On day 7, expression of β III-tubulin was lower on the β-NGF + PBS side than on the control side, and that of neurofilament 160 was greater. On day 14, β III-tubulin and protein gene product 9.5 were greater on the β-NGF + PBS side than on the control side. Vascular endothelial growth factor expression was greater on the experimental side than the control side at 7 days, and vascular endothelial growth factor receptor 2 expression was elevated on days 14 and 21, but lower than control levels on day 28. However, no difference in the number of blood vessels was observed between sides. Our results indicate that topical application of β-NGF promoted neurogenesis, and may modulate angiogenesis by promoting nerve regeneration in collagen bone substitute-filled defects.

Key words: nerve regeneration, β-nerve growth factor, collagen, angiogenesis, protein gene product 9.5, vascular endothelial growth factor, &beta, III-tubulin, neural regeneration