直接延长损伤神经断端本身修复周围神经缺损的机制研究

Autogenous nerve grafts had been regarded as the current "gold standard" for repairing a segmental peripheral nerve defect. However this technique causes a donor site morbidity such as the sacrifice of healthy nerves, sensory loss, and formation of a painful neuroma, and the amount of suitable graft materials are limited. Because of these reasons, other alternative methods, such as the allograft, artificial tubes, vein grafts, and arterial grafts have been investigated for the autogenous nerve grafting. Nevertheless none of techniques to date have surpassed effectiveness of the autogenous nerve grafting. We have developed a new method for repairing the segmental peripheral nerve defects. With such a method, an end-to-end neurorrhaphy was performed directly following a gradual lengthening of nerve stumps. Our previous studies showed that a nerve regeneration after the repair of a nerve defect by this method shown to be better than the autogenous nerve grafting. However the mechanism of nerve regeneration is still unknown. Therefore, we propose a hypothesis: it might improve the proliferation of Schwann cells when the nerve stump is lengthened gradually. Then GAP-43 and NCAM, that secreted by Schwann cells, were increased, to improve the activity of chemotaxis as a guidance of regeneration axons. Nerve lengthening may also promote the regeneration of new blood vessels, which can improve nerve regeneration. Nerve lengthening to promote axon regeneration may also be related to IL -1 gene regulation. To confirm these hypotheses, we will analyze the change of GAP - 43, NCAM, the reconstruction of blood supply and IL -1 gene regulation, to explore the mechanism of nerve regeneration in the repair process. This study would provide a theoretical basis for the clinical application of this new method.

目前治疗周围神经缺损的黄金标准是自体神经移植，但由于供体神经来源有限，常常在临床应用中受限。于是我们开发了不需要供体神经的新方法- - 神经断端直接延长法。此方法通过直接延长损伤神经的断端本身，促使轴索不断再生，直至神经间隙消失后，行神经端-端吻合术来修复神经缺损的方法。我们的前期实验结果提示：此方法对于一定程度的神经缺损的修复效果优于自体神经移植。但其修复机制还有待进一步探讨。为此，我们提出假说：通过牵拉神经断端可能使施万细胞本身及其分泌的GAP-43、NCAM对再生轴索的趋化作用、接触引导作用加强。神经延长还可能促进新生血管的再生，使再生轴索有良好的血供。神经延长促进轴索再生作用可能还与整合素家族IL-1的基因调控有关。为了验证这一假说我们通过分析神经牵拉过程中GAP-43，NCAM的动态变化、血供重建、IL-1基因调控改变，探讨修复过程中的具体机制，为此新技术的临床应用提供理论依据。

周围神经损伤一直是骨科领域中常见的损伤之一，神经缺损的修复是一项尚未攻克的难题。目前治疗周围神经缺损的黄金标准是自体神经移植，但两处吻合口对神经再生不利，加上要牺牲自体一条神经，导致供区的功能障碍（感觉丧失、瘢痕或可能引起痛性神经瘤），且自体神经来源有限，遇到长段直径粗大的神经缺损或多发性神经缺损，自体神经移植受到限制。因此，我们开发了神经断端直接延长法。此方法不需要牺牲自身正常神经（供体神经），不引发神经供区的并发症，它对神经的延长是直线延长，不会压迫神经。我们的前期实验结果提示：此方法对于一定程度的神经缺损的修复效果优于自体神经移植。为了把神经断端直接延长法修复周围神经缺损应用于临床，我们设计了适用于临床及大型动物的神经延长器，进一步探讨此方法对于长段神经缺损的修复以及进一步研究缓慢牵拉刺激在神经再生修复过程中是否引起神经细胞体的损伤，更好的完善组织工程修复，为实际操作提供理论依据。