神经生长因子对挤压伤坐骨神经再生的促进作用

背景神经生长因子(nervegrowth factor,NGF)不仅是维持促进中枢神经系统发育、分化、存活的基本的生长因子,而且在外周神经损伤的修复中也起着重要的作用.目的观察NGF肌注对大鼠坐骨神经挤压伤后神经再生恢复以及功能的影响.设计以实验动物为研究对象,随机对照的重复观察测量,探索性研究.单位一所军医大学的新药评价中心.材料实验于1999-07/2000-03在第二军医大学基础部新药评价中心完成.SD大鼠40只,雌雄各半,体质量200～250g,上海西普尔-必凯实验动物有限公司提供.方法将40只大鼠随机分成NGF高、中、低剂量组,正常对照和模型对照组.距坐骨切迹远端6mm处钳夹坐骨神经,使产生-4 mm宽的挤压伤.NGF高、中、低剂量组分别给予NGF8,4和2μg/kg(1.6×103,8×102和4×102 IU/kg)药物,肌注1次/d,连续56 d.主要观察指标①手术后的不同时间神经传导速度(nerveconduction ve1ocities,NCV)和坐骨神经功能指数(sciatic functional index,SFI).②组织形态学评价.结果与模型对照组相比,高剂量组在35,56d,中剂量组在35 d的NCV均显著加快(t=2.32～5.14,P＜0.05～0.01);高、中、低3个剂量组在手术14d后的SFI与模型组相比,差异均有显著性意义(t=2.29～6.28,P＜0.05～0.01),且高剂量组恢复较明显,至56d各剂量组SFI各组差异均无显著性意义;组织形态学显示,NGF治疗组神经髓鞘、轴索与正常对照组相比,差异无显著性意义;而模型组髓鞘出现脱失,细微结构不清晰,许旺细胞变性坏死.结论NGF对大鼠坐骨神经受损部位的神经髓鞘及轴索有明显的改善作用,能促进其神经纤维的再生及神经功能的恢复.

Promoting effect of nerve growth factor on sciatic nerve regeneration after the crush injury

BACKGROUND: Besides being a basic growth factor crucial to maintain and promote the development, differentiation and survival of the central nervous system, nerve growth factor(NGF) also plays an important role in the repair of injured peripheral nerves.OBJECTIVE: To investigate the effect of the muscular injection of NGF on the regeneration and functional recovery of rat sciatic nerve after crush injury.DESIGN: A randomized controlled pilot study in rats with repeated observation and measurement.SETTING: Center for new drug evaluation in a military medical university.MATERIALS: This study was performed in the Center for New Drug Evaluation, Department of Basic Medicine, Second Military Medical University during the period from July 1999 to March 2000, using 40 SD rats weighing 200 to 250 g(of either sex of half number) provided by the Sino-British SIPPR/BK Lab Aninal Ltd (Shanghai).METHODS: Forty rats were randomized into high-, mid- and low-dose NGF treatment groups, normal control group and model control group. The sciatic nerves were clamped at 6 nm distal to the sciatic notch to induce a 4-mm-wide area of crush injury. In the high-, mid-; and low-dose NGF groups, the rats were given NGF at 8, 4 and 2 μg/kg per day(corresponding to 1.6 × 10 3, 8 × 10 2 and 4 × 10 2 IU/kg per day) respectively via the muscular injection for 56 consecutive days.(NCVs) and sciatic function index(SFI) at different time points after the RESULTS: Compared with that of the model control group, the NCVs significantly increased in the high-dose NGF group 35 and 56 days after the injury,and in the mid-dose NGFgroup at 35 days(t=2.32-5.14, P ＜0.05-0.01 ). The SFIs significantly increased in all NGF-treated groups at 14 days ( t = 2. 29-6.28, P ＜ 0.05-0.01 ), with the recovery most conspicuous in high-dose NGF group; No significant difference in the SFIs was found between the NGF-treated groups on the 56th day. Morphological examination of the tissues identified no significant difference in the nerve myelin sheaths and axons in NGF-treated groups as compared with the normal control group,while in the model control group, myelin sheath dislocation with unclear microstructure was observed, accompanied by Schwann cell degeneration and necrosis.CONCLUSION: NGF promotes the repair of the damaged nerve myelin sheath and axon and stimulates nerve fiber regeneration and function recovery of the crushed rat sciatic nerves.