局部应用GDNF对运动神经的保护作用研究_临床医学论文.docVIP

局部应用GDNF对运动神经的保护作用研究_临床医学论文 局部应用GDNF对运动神经的保护作用研究_临床医学论文 【摘要】 　　目的 研究周围神经损伤后，经蛛网膜下腔置管局部应用外源性胶质细胞源性神经营养因子(glial cell line，GDNF)对脊髓前角运动神经元的保护作用。方法 成年SD大鼠随机分为两组，即手术加生理盐水组和手术加GDNF组。切断大鼠坐骨神经致相应脊髓前角运动神经元损伤，于L5、6腰椎椎间隙行蛛网膜下腔置管，并注入外源性GDNF(10 μg/mL)，分别与术后4、8、12周行神经功能指数检测；于不同时间处死动物并取材，对L4～6节段脊髓标本冰冻切片，行尼氏体染色、光镜检查，并于术后12周取坐骨神经，行电镜检查并采用图象分析仪检测有髓神经纤维数目、髓鞘厚度和轴突直径。结果 GDNF组的坐骨神经功能指数、脊髓前角运动神经元的存活率、有髓神经纤维数目、髓鞘厚度和轴突直径均优于对照组，经统计学处理，两组差异有显著性(P＜0.05)。结论 通过蛛网膜下腔注入外源性GDNF保护相应的脊髓运动神经元的同时也促进外周神经功能的恢复。 【关键词】 周围神经 损伤 运动神经元 胶质细胞源性神经营养因子 　　Abstract：Objective To investigate the effect of exogenous glial cell linere randomly divided into 2 groups：NS group and GDNF group.The left sciatic nerve in rats were cut off.And then 0.9％ saline and GDNF solution were injected into cavitas subarachnoidealis at L4～6 in NS group and GDNF group，respectively.The rats were sacrificed on postoperative day 4w，8w and 12w respectively.Their specimen of L4～6 spinal cord were taken at different time and sectioned.The Nissl staining in motor neurons were used for counting of motor neurons.Electron microscopic observation and morphometric analysis were performed at 12 weeks after operation.Results In GDNF group the number of motor neurons in spinal front corner higher than that of NS group.The mean axon diameters and mean myeline sheath thickness were significantly better in GDNF group than control group.SFI in GDNF group was lower in NS group.Conclusion The exogenous GDNF infused into the cavitas subarachnoidealis are supposed to protect the degenerated spinal motor neuron from death after sciatic nerve injury，and to encourage the periphery nerve recovery. 　　Key word：peripheral nerve；injury；motor neuron；glial cell linederived neurotrophic factor(GDNF) 　　周围神经损伤可引起神经近端发生“轴突反应”，造成相应脊髓神经元胞体出现一系列形态、生化功能和代谢上的变化，严重时引起胞体的凋亡［1］。周围神经损伤后再生的先决条件是神经元胞体的存活及轴突的延伸，而后两者又有赖于微环境中神经生长因子的浓度。胶质细胞源性神经营养因子(glial cell line，GDNF)是近年发现的重要神经营养因子(neurotrophicfactor，NTF)，是目前特异性最强的多巴胺能NTF，对运动神经元和感觉神经元均有强大的神经营养作用［2］。本实验旨在通过切断并显微吻合坐骨神经造成动物脊髓前角运动神经元损伤，经蛛网