同轴共纺复合神经生长因子导管修复大鼠坐骨神经缺损的实验研究

Compound nerve conduit promoting peripheral nerve regeneration in rats

目的观察同轴共纺复合神经生长因子（NGF）导管对大鼠坐骨神经缺损修复的促进作用。方法以复合NGF的牛血清白蛋白为芯层、乳酸-己内酯共聚物[P（LLA—CL）]为壳层，采用同轴共纺技术制备具有“壳-芯”结构的可降解纳米纤维复合神经导管。取sD大鼠72只，随机分为四组：自体神经移植组（A组），单纯[P（LLA—CL）]导管组（B组），单纯导管内一次性注射NGF组（C组）和复合NGF导管组（D组），每组18只。制作大鼠坐骨神经10mm缺损模型，四组大鼠分别采用自体神经移植、单纯[P（LLA—CL）]导管、单纯导管内一次性注射NGF、复合NGF导管桥接修复缺损。于术后第1、2、3个月行大体观察、坐骨神经功能指数、小腿三头肌湿重恢复率测量、电生理检测和组织学检查。结果术后复合NGF导管逐渐开始吸水膨胀并降解，3个月时，虽然管壁已经出现裂隙，但依然保持良好的外形，没有对再生神经形成卡压。术后1个月，再生神经均已通过缺损，连接两断端，但较细小；随着时间的延长，再生神经逐渐增粗。各组间比较发现，D组再生神经取得了和A组相似的效果，明显优于B组和C组（P〈0．05）。尽管D组与A组之间比较，差异无统计学意义（P〉0．05），甚至D组的有髓神经纤维计数还稍高于A组，但其髓鞘的厚度和直径不如A组，并且坐骨神经功能指数和腓肠肌湿重恢复率也比A组稍差。结论同轴共纺复合NGF神经导管具有良好的组织相容性、生物活性和机械强度，能够有效地促进神经再生，效果接近自体神经移植。

Objective To explore the role of compound nerve conduit, made of nerve growth factors （NGF） encapsuled by biodegradable core-shell nanofibers through coaxial electrospinning, in regeneration of injured sciatic nerves in rats. Methods The compound nerve conduits were developed from the core-shell structured biodegradable nanofibers with P（LLA-CL） as a shell and BSA/NGF or BSA as a core through coaxial electrospinning. Seventy-two Sprague-Dawley rats were randomly divided into 4 even groups. The middle segments （10 mm） of the sciatic nerve were excised and the defects were repaired with sciatic nerve autograft （group A）, with P（LLA-CL） conduit （group B）, with PLLA-CL conduit and one injection of NGF （group C）, and with P（LLA-CL）/NGF controlled-release conduit （group D）, respectively. Morphologie and functional evaluations of nerve regeneration were done by gross observation, sciatic function index, neural electrophysiological examination, resumption rates of triceps weight, histological and ultrastructural observation respectively in 1, 2, 3 months after the operation. Results Three months after the operation, although partial biodegradation and small cracks could be observed, conduits remained intact in outline. Based on the functional and histological observations, nerve regeneration, nerve fibers arrangement, myelination and nerve function reconstruction in the P（LLA-CL）/NGF controlled-release conduit （group D） were similar to those in nerve autograft （group A ） and significantly superior to those in groups B and C （ P 〈 0.05 ） . Conclusion As the P（LLA-CL）/NGF-controlled release conduit has favorable mechanical properties and biocompatibility, it can effectively promote regeneration of the sciatic nerve in rats.