壳聚糖复合他克莫司缓释鞘管促进大鼠坐骨神经再生的实验研究

目的观察壳聚糖复合他克莫司(FK506)缓释鞘管结合3mm小间隙桥接神经对神经再生的影响。方法将45只雄性SD大鼠,随机分成3组,切断双侧坐骨神经制成坐骨神经再生室模型,并保留断端间隙为3mm。实验所用得桥接材料分别是:硅胶管、壳聚糖鞘管、壳聚糖复合FK506缓释鞘管。分别于术后6、8、12周观察桥接材料周围的瘢痕形成及吸收情况,并行神经电生理、组织学观察、图象分析、腓肠肌湿重检测比较各组大鼠坐骨神经的再生与功能恢复情况。结果术后大体标本观察显示:对照组再生室与周围组织粘连较重;壳聚糖鞘管组、壳聚糖复合FK506鞘管组神经桥接处较易与周围组织剥离,粘连轻微。6周时各组再生室均尚存;8周时壳聚糖鞘管组、壳聚糖复合FK506鞘管组桥接材料开始吸收;12周时壳聚糖鞘管组、壳聚糖复合FK506鞘管组桥接材料不完整或仅有碎片残留,神经连续性建立,且与周围组织无明显粘连。评估神经再生的运动神经传导速度、复合肌肉动作电位、潜伏期检测指标,壳聚糖复合FK506鞘管组(10.2m/s±0.8m/s、4.3mV±0.3mV、1.9ms±0.4ms)明显优于对照组(4.2ms±0.5ms、1.2mV±0.3mV、7.5ms±0.4mV)、壳聚糖鞘管组(9.5ms±0.3ms、2.7mV±0.3mV、3.1ms±0.4ms),P<0.05。壳聚糖鞘管组虽然各指标均数优于对照组,但之间差异无统计学意义。结论应用壳聚糖复合FK506缓释鞘管桥接大鼠坐骨神经,在体内稳定2个月以上开始降解,能够明显促进神经再生与功能恢复,且降解产物为多糖类,不影响神经再生微环境。

Favorable effect of chitosan sustained-release FK506 incorporated conduits on axonal regeneration in rat sciatic nerve

Objective To investigate the efficacy of 3 mm gap bridging repairing neurotmesis with chitosan sustained-release FK506 incorporated conduits. Methods Forty-five adult male SD rats were divided randomly into 3 groups. The rats were received a neurotomy to bilateral sciatic nerve and subsequently reconnected with regeneration chambers. The bridging conduits of group A, B and C were made of silicon tube, chitosan and chitosan sustained-release FK506 incorporated respectively. Conduits absorption and surrounding tissue cicatrization were observed at 6, 8 and 12 weeks after neurotomy. The nerve regeneration and functional recovery were evaluated by electrophysiology, histological changes, morphometric analysis, and weighing of gastrocnemius muscles. Results The silicon tubes of group A adhered severely with surrounding tissue. Bridging grafts of group B and C adhered relatively slightly and could be stripped easily from surrounding tissue. The regeneration chambers still existed fully at 6 weeks and began to be degradated at 8 weeks after neurotomy. The bridging grafts of group B and C were disintegrated at 12 weeks and the continuity of sciatic nerve was established without obvious adhesion with surrounding tissue. The statistical evaluation for nerve regeneration demonstrated that rats of group C showed the best results. Although rats of group B and A were found to be the second and the third respectively, there is no significant difference between them. Conclusion Remaining 3 mm gap bridging repairing rat sciatic nerve with chitosan sustained-release FK506 incorporated conduits, which stabilize for more than 2 months before degradation in vivo, can significantly promote nerve regeneration and facilitate function recovery without adverse effects.