大鼠坐骨神经切除后人发角蛋白诱导的神经的再生机制  

Mechanism of rat sciatic nerve regeneration induced by human hair keratin

作　　者：胡莲美[1] 朴仲贤[2] 王启伟[3] 王万山[4] 顾为望[4] 朴英杰[4] 

机构地区：[1]解放军第458医院肝病重点实验室,广东广州510602 [2]汕头大学医学院中心实验室,广东汕头515041 [3]军事医学科学院生物工程研究所,北京100071 [4]南方医科大学比较医学研究所,广东广州510515

出　　处：《南方医科大学学报》2008年第7期1136-1140,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(30300191);广东科技计划专项(2003A3020101)

摘　　要：目的观察人发角蛋白(HHK)诱导坐骨神经再生时的形态学变化,以揭示神经再生机制。方法制备坐骨神经损伤动物模型,植入HHK丝束桥接体,于术后2天、1、2、3、6、9、12周进行组织学观察。结果术后第2天到2周,大量新生微血管长入HHK植入部位,切除后近远端的施万细胞发生去分化。去分化后的施万细胞沿着HHK丝束表面纵向分裂增殖。术后第3周人发开始降解,HHK周围可见很多巨噬细胞和多核巨细胞,大量增生的施万细胞有规则地排列于HHK丝间,有轴突和大量的微血管出现。术后第6周,在HHK丝周围可见大量新生的神经纤维,其间有微血管分布。术后第9周,人发角蛋白降解显著,再生神经纤维增多,有明显的神经外膜和束膜。术后第12周,实验组人发角蛋白基本完全降解,其部位被新的神经纤维所取代,并已贯通缺损部位,且外观形态接近正常神经。结论1、HHK对缺损的坐骨神经修复具有良好的桥接作用。2、受损后高度分化的施万细胞通过去分化形成幼稚的施万细胞,其中胞质脱落起着关键作用。3、受损轴突立即发生保护性封闭、脱落。健康轴突形成膨大的带突起的生长锥,生长锥突起上伸出许多丝状生长芽,并与1到多个施万细胞嵌合,它们通过竞争性选择,最后只有一条生长芽可发育成完整的轴突。4、神经纤维屏障膜(神经外膜、束膜及内膜)是由最外侧的血管屏障膜中和束内的微血管间充质细胞演变而成的。总之,施万细胞、神经轴突、神经膜三者的再生模式是自身器官化过程所要求的,它们是同步进行的协调行为。Objective To evaluate the effect of human hair keratin （HHK） in peripheral nerve repair and explore the mechanism of sciatic nerve regeneration. Methods Rat models of sciatic nerve damage was established by creating a 10-mm gap in the sciatic nerve, which was bridged with a HHK implant. Histological examinations of the nerve tissues were performed at different time points after the surgery. Results During the period from 2 days to 2 weeks following HHK implantation, Schwann cells were found to undergo dedifferentiation and proliferate along the HHK implant. Three weeks after HHK implantation, numerous macrophages and megakaryocytes occurred around the HHK, and a large quantity of regenerated Schwann cells aligned in orderly fashion was seen between the fine filaments of partially degraded HHK, where axons and capillaries were also observed. Six weeks later, massive nerve fibers and capillaries developed around the HHK, and at 9 weeks, the HHK implant was substantially degraded and numerous regenerated nerve fibers occurred characterized by obvious epineurium and perineurium. Till 12 weeks after HHK implantation, HHK was almost completely degraded and replaced by the newly regenerated nerve fibers that had grown across the nerve defect. Conclusions HHK is an ideal material for nerve injury repair. Apocytosis plays a key role in the differentiation process of highly differentiated Schwann cells into immature Schwann cells following nerve injury. As a protective mechanism, the axons undergo enclosure and dissociation following injuries, and the intact axons give rise to growth cones that extend fibers of growing buds to competitively bind the one or more Schwann cells, but only one such but finally develops into a complete axon. The nerve fiber barrier membrane is derived from the capillary menchymal stem cells and the outmost vascular barrier membrane. The regeneration of the Schwann cells, axons and the nerve membrane is the result of self-organization through a well synchronized and coordinated mechanism.

关 键 词：人发角蛋白 坐骨神经损伤/修复 屏障膜 

分 类 号：R651.3[医药卫生—外科学]