中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (6): 976-981.doi: 10.4103/1673-5374.150744

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

N-丙酰甘露糖胺刺激损伤坐骨神经轴突延长：小鼠体内研究验证

  

  • 收稿日期:2015-02-16 出版日期:2015-06-18 发布日期:2015-06-18

N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic nerve injury

Christian Witzel 1, Werner Reutter 2, G. Björn Stark 3, Georgios Koulaxouzidis 3   

  1. 1 Plastic and Reconstructive Surgery, Interdisciplinary Breast Center, Charité – Universitätsmedizin Berlin, Germany
    2 Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité – Universitätsmedizin Berlin, Germany
    3 Department of Plastic and Hand Surgery, University of Freiburg Medical Centre, Freiburg, Germany
  • Received:2015-02-16 Online:2015-06-18 Published:2015-06-18
  • Contact: Christian Witzel, M.D., christian.witzel@charite.de.

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摘要：

N-丙酰甘露糖胺促进体外神经突生长和功能性突触重建。为研究N-丙酰甘露糖胺系统应用对坐骨神经损伤小鼠模型的影响，实验用未经荧光蛋白标记的坐骨神经移植桥接黄色荧光蛋白标记的坐骨神经缺损。在移植前后各5 d腹腔注射全乙酰化N-丙酰甘露糖胺或生理盐水。神经移植后5 d，腹腔注射N-丙酰甘露糖胺的小鼠坐骨神经轴突再生距离和有分支轴突数量均较注射生理盐水小鼠明显延长和增加，但N-丙酰甘露糖胺不影响再生轴突数量和每个分支轴突的分支数量。N-丙酰甘露糖胺有促进损伤周围神经再生的作用。

关键词: 神经再生, N-丙酰甘露糖胺, 唾液酸, 糖化工程, 坐骨神经, 周围神经, 分支, Thy1-YFP小鼠

Abstract:

Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modified in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp) increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the influence of systemic ManNProp application using a specific in vivo mouse model. Using mice expressing axonal fluorescent proteins, we quantified the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow fluorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg) or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection). ManNProp significantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm; P < 0.005) and the number of arborizing axons (21% vs. 16%; P = 0.008) 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoengineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration.

Key words: N-propionylmannosamine, sialic acid, glycoengineering, sciatic nerve, peripheral nerve, branching, arborisation, Thy1-YFP mouse, nerve regeneration