胶质细胞源性神经营养因子基因修饰的雪旺氏细胞修复大鼠周围神经缺损的实验研究

An experiment study on repair of peripheral nerve defects by GDNF gene modified Schwann cells

目的 从转基因角度探讨治疗周围神经损伤的有效方法。方法 成年Wister大鼠 4 8只 ,平均分为 3组。切断大鼠坐骨神经并形成 10mm长缺损 ,用硅胶管桥接两侧断端 ,管腔内植入胶质细胞源性神经营养因子 (glialcell linederivedneurotrophicfactor,GDNF)修饰的雪旺氏细胞 (schwanncells,SCs) ,正常SCs修复组和单纯硅胶管修复组作为对照 ,分别于术后 4、8、12和 16周对各组动物进行大体观察 ,肌电图测量 ,组织学切片观察 ,再生神经的神经电生理检测 ,GDNF免疫组化检测 ,组织学切片 ,观察和图像分析。结果 GDNF SCs组动物的神经传导速度、有髓神经纤维密度、神经组织面积、髓鞘厚度均显著优于SCs组和硅胶管组。结论 将GDNF基因修饰的雪旺氏细胞移植修复周围神经缺损 ,使局部释放的GDNF维持神经元存活 ,加快轴突再生速度以促进周围神经再生 ,此方法为将来治疗周围神经损伤提供了线索。

Objective To investigate an effective treatment of peripheral nerve injuries by means of gene transference. Methods 48 adult Wister rats were divided evenly into 3 groups.A 10 mm sciatic nerve gap was created and bridged with a silicone chamber.The silicone chamber was filled with glial cell-line derived neurotrophic factor(GDNF) gene modified Schwann cells(SCs)(group 1),the normal SCs(group 2) and nothing(the control).At 4,8,12,and 16 weeks after the operation,the general and histological observations,the electromyographic and immunohistochemical examinations were performed to the regenerated nerves. Results The GDNF-SCs group was significantly better than the SCs and the control groups in nerve conduction velocity,the number and density of reinnervation,the area of regenerated nerve and the thickness of myelin sheath of the regenerated nerves. Conclusion GDNF gene modified SCs secrete higher levels of neurotrophic factors for a prolonged time,which are more effective in peripheral nerve repair than the normal SCs.