Early nerve regeneration after Achilles tendon rupture - a prerequisite for healing? A study in the rat
Early nerve regeneration after Achilles tendon rupture - a prerequisite for healing? A study in the rat
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DOI：
10.1016/s0736-0266(01)00159-0
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发表时间：
2002-07-01
影响因子：
2.8
通讯作者：
Kreicbergs, A
中科院分区：
文献类型：
--
作者：
Ackermann, PW;Ahmed, M;Kreicbergs, A
应用免疫组织化学方法对大鼠跟腱断裂愈合过程中的神经再生进行了半定量研究。再生和成熟纤维的神经元标记物，即，在破裂后不同时间点（1-16周）分别分析生长相关蛋白43（GAP-43）和蛋白基因产物9.5（PGP 9.5）。在腱旁，断裂和完整的对侧肌腱（对照）始终表现出免疫反应的两个神经元标记。然而，在适当的肌腱组织中，只有断裂的肌腱对GAP-43和PGP 9.5呈免疫反应性。这种表达在破裂后第1周就已经观察到，在第6周达到峰值，随后连续下降直到第16周。此外，根据降钙素基因相关肽（CGRP）和神经肽Y（NPY）的免疫反应性的感觉和自主神经纤维的发生，分别进行了分析。从2-6周开始，在血管周围和正在愈合的适当肌腱组织中发芽的游离神经末梢中大量观察到CGRP阳性。NPY出现较晚，在破裂后6-8周，主要位于血管周围的疏松结缔组织中。除了在血管作用中的作用（CGRP，血管舒张; NPY，血管收缩）之外，两种神经肽都涉及血管生成所需的成纤维细胞和内皮细胞增殖。目前的研究表明，早期愈合的肌腱断裂的特点是一个精心策划的，时间出现的神经纤维表达肽与不同的行动。观察到的神经元再生和神经肽表达的模式可能被证明是重要的正常结缔组织愈合。(C)2002骨科研究学会。由Elsevier Science Ltd.出版，版权所有。
Nerve regeneration during healing of Achilles tendon rupture in the rat was studied by immunohistochemistry including semi-quantitative assessment. Neuronal markers for regenerating and mature fibers, i.e., growth associated protein 43 (GAP-43) and protein gene product 9.5 (PGP 9.5), respectively, were analyzed at different time points (1-16 weeks ) post-rupture. In the paratenon, both the ruptured and intact contralateral tendon (control) consistently exhibited immunoreactivity to the two neuronal markers. However, in the proper tendinous tissue only the ruptured tendon showed immunoreactivity to GAP-43 and PGP 9.5. this expression was seen already at week 1 post-rupture to reach a peak at week 6 followed by a successive drop till week 16. Also the occurrence of sensory and autonomic fibers according to immunoreactivity for calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY), respectively, was analyzed. CGRP-positivity was abundantly seen from weeks 2-6 in both perivascular and sprouting free nerve endings in the proper tendon tissue undergoing healing. NPY appeared later, at weeks 6-8 post-rupture around blood vessels mainly located in the surrounding loose connective tissue. Apart form a role in vasoaction (CGRP, vasodilatory; NPY, vasoconstrictory), both neuropeptides have been implicated in fibroblast and endothelial cell proliferation required for angiogenesis. The present study shows that early healing of ruptured tendons is characterized by an orchestrated, temporal appearance of nerve fibers expressing peptides with different actions. The observed pattern of neuronal regeneration and neuropeptide expression may prove to be important for normal connective tissue healing. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.