胶质细胞源性神经营养因子基因修饰的雪旺细胞对大鼠坐骨神经缺损的修复作用  

Effects of glial cell line-derived neurotrophic factor modified Schwann cells on repair of sciatic nerve defects in rats

作　　者：张文捷[1] 周跃[1] 陈菁[2] 王建忠[1] 陈建梅[2] 

机构地区：[1]第三军医大学新桥医院骨科,重庆400037 [2]第三军医大学野战外科研究所6室

出　　处：《中华手外科杂志》2004年第3期186-188,F003,共4页Chinese Journal of Hand Surgery

基　　金：国家自然科学基金资助项目 (30 1 70 96);国家 973基金资助项目 (G1 9990 542 0 6)

摘　　要：目的　研究胶质细胞源性神经营养因子 (glialcellline derivesneurotrophicfactor ,GDNF)基因对周围神经断伤后促进轴突再生及神经元的保护作用。方法　应用体外获取的GDNF修饰的雪旺细胞结合细胞外基质凝胶及生物可降解聚乳酸 聚羟基乙酸共聚物管 (polyCDL lactide co glycolide ,PLGA)构建的神经移植复合体 ,修复大鼠坐骨神经的缺损。 2 0只成年Wistar大鼠按桥接物的不同随机分为 4组 ,每组 5只。A组 :细胞外基质凝胶 PLGA管桥接组 ;B组 :雪旺细胞 细胞外基质凝胶 PLGA管桥接组 ;C组 :GDNF基因修饰的雪旺细胞 细胞外基质凝胶 PLGA管桥接组 ;D组 :自体神经桥接组。术后 12周检测运动神经传导速度 ,并进行再生神经的组织形态学观察以及计量学分析。结果　术后 12周 ,坐骨神经的运动神经传导速度 ,轴突数、髓鞘的厚度、神经纤维的直径、神经组织面积的百分比和脊髓前角运动神经元存活率等 ,C组均优于A、B组 (P <0 .0 1) ,而与D组相比无明显差异 (P >0 .0 5 )。结论　雪旺细胞的转基因处理可能弥补单纯细胞移植神经营养因子含量的不足 ,而达到与自体神经移植相似的效果。Objective To investigate the effects of glial cell line-derives neurotrophic factor (GDNF) modified gene on facilitating nerve regeneration and protecting neuronal survival after the peripheral nerve transection in rats. Methods The nerve grafts was constructed by schwann cells modified with GDNF harvesting from ex vitro, combined with extracellular gel and biodegradable polyCDL-lactide-co-glycolide (PLGA) conduit. The sciatic nerve was bridged by the grafts. Twenty adult Wistar rats were divided into 4 groups randomly, with 5 in each. Group A: extracellular matrix gel and PLGA conduits, group B: Schwann cells, extracellular matrix gel and PLGA conduits, group C: GDNF-modified Schwann cells, extracellular matrix gel and PLGA conduits, group D: autografts. Motor nerve conduction velocity(MNCV) and morphology of regenerated axons were investigated on 12 week postoperatively. Results Compared with group A and B, there was higher rates in group C in MNCV, the number and thickness of axon, the diameter of nerve fiber, the percentage of the nerve tissue area, and survival rate of motoneuron in the ventral horn in spinal cord. But there is no significant difference when the index was compared with those in group D. Conclusion These results suggest that using Schwann cells gene transfer techniques can make up the shortage of the lower content in neurotrophic factors from simple cell transplantation. The result can be comparable to that of autografts.

关 键 词：雪旺细胞 PLGA 细胞外基质 胶质细胞源性神经营养因子 成年WISTAR大鼠 坐骨神经缺损 运动神经传导速度 GDNF基因 转基因 轴突 

分 类 号：R651[医药卫生—外科学] R318[医药卫生—临床医学]