PNGF导管复合骨髓间充质干细胞修复大鼠12 mm坐骨神经缺损

目的　观察RGD多肽接枝聚（乳酸-羟基乙酸-L-赖氨酸）/聚乳酸/β-磷酸三钙/神经生长因子（PRGD/PDLLA/β-TCP/NGF，PNGF）缓释导管复合骨髓间充质干细胞(Bone marrow derived mesenchymal stem cells, BMSCs)构建组织工程化人工神经，修复大鼠12 mm坐骨神经缺损的效果。  方法    雄性Wistar大鼠30只, 随机分为3组，每组10只，左后肢制作12 mm坐骨神经缺损模型，分别行单纯PNGF导管桥接（A）、PNGF导管复合BMSCs桥接（B）、自体神经移植（C），所有大鼠左侧为实验侧，右侧为正常自身对照侧。术后3个月行大体观察、坐骨神经功能指数、电生理检测、小腿三头肌湿重恢复率测量、新生神经及靶肌肉组织学观察等检测坐骨神经功能恢复情况。  结果　术后3个月取材时见导管管壁变薄，表面血管化良好，管内有再生神经通过，直径较正常神经细。坐骨神经功能指数的检测结果显示PNGF导管复合BMSCs高于单纯PNGF导管组（P＜0.05），PNGF导管复合BMSCs组神经传导速度恢复率、小腿三头肌湿重恢复率、有髓神经纤维数量和直径均优于单纯PNGF导管组（P＜0.01），取得与自体神经移植组相似的效果。  结论　PNGF缓释导管复合BMSCs桥接修复大鼠坐骨神经缺损, 能够有效促进神经再生, 效果接近自体神经移植。

PNGF conduit seeded with bone marrow derived mesenchymal stem cells to repair 12-mm sciatic nerve defect of rat

Objective　To evaluate the effectiveness of tissue-engineered artificial nerve consists of novel arginine-glycine-aspatic acid (RGD) peptide modification of poly{(lactic acid)-co-(glycolic acid)-alt-(L-lysine)]}/poly(d,l-lactic acid)/β-tricalcium phosphate/nerve growth factor(PRGD/PDLLA/β-TCP/NGF,PNGF) sustaining release conduit seeded with Bone marrow derived mesenchymal stem cells(BMSCs) in bridging 12-mm sciatic nerve defect in rats.　Methods　30 isogenic adult male Wister rats were randomly divided into 3 groups (n=10 in each), the left sciatic nerve was exposed to create a 12-mm gap in all rats. Animals in the three groups were bridged with PNGF conduits (A), PNGF conduits filled with BMSCs(B) and autografts, respectively. The left was the experimental side and the right was the normal, intact control. At three months after the operation, recovery rate of wet weight of triceps suraes, histological observation of regenerative nerve and target muscle tissue were performed to evaluate the functional recovery of sciatic nerve.　Results　The conduit wall became thinner three months after the operation, continuously regenerated nerve tissue was located in the conduit, and the surface of regenerated nerve can be observed with creeping growth of nutrient vessels. All regenerated nerves were thinner than normal, intact nerves. The result of SFI in Group B was superior to that of Group A, and the difference was statistically significant(P＜0.05);  the recovery rate of nerve conduction velocity, the recovery rate of weight triceps surae, the number of myelinated nerve fibers and thickness of myelin sheath in Group B were significantly higher than those in Group A(P＜0.01), acquiring similar results to that of autologous nerve transplantation group.   Conclusion    PRGD/PDLLA/β-TCP/NGF composite nerve conduit seeded with Bone marrow derived mesenchymal stem cells can effectively promote nerve regeneration after bridging sciatic nerve defect in rats. The effect was as good as that of autograft.