目的 探讨不同时间段使用他克莫司(FK506)纳米微球在同种异体移植后促进神经的再生作用.方法 采用单乳化-溶剂挥发法(O/W)制备FK506纳米微球,同种异体移植大鼠胫神经.A组术后立即局部应用FK506纳米微球,B组24 h给药,C组3 d后给药,D组不给药;于术后第4、8和12周行移植神经大体观察、组织学检查及有髓纤维图像分析、小腿三头肌湿重测定、荧光素逆行标记神经元、双侧胫神经电生理比较.结果 FK506纳米微球降解快、吸收好.A、B组神经再生效果相似,都明显要比C、D组好,差异有统计学意义;C、D组之间差异也有统计学意义.结论 FK506纳米微球释药速度符合神经损伤后再生规律,局部应用有良好的促进神经再生作用,而且早期(24 h内)给药效果更加明显.%Objective To study the effect of the application of P(DLLA-co-TMC)/FK506 microspheres at different intervals on peripheral nerve regeneration after tibial nerve allograft. Methods P (DLLA-coTMC)/FK506 microspheres were fabricated using an oil-in-water single emulsion and solvent evaporation method.Tibial nerve allograft model was created in mice which were divided into group A, B, C and D. In groups A, B and C were P( DLLA-co-TMC)/FK506 microspheres were administered locally on the day of surgery, 24 hours postoperatively, and 3 days postoperatively, respectively. Group D was left untreated. On postoperative weeks 4,8 and 12, gross observation of the graft, histomorphometric image analysis, triceps surae wet weight,retrograde tracing and fluorescence microscopy of motor neurons, and electrophysiological examination of bilateral tibial nerves were carried out. Results P (DLLA-co-TMC)/FK506 microspheres degraded fast and were well absorbed. There was a statistically significant improvement in neuroregeneration in groups A and B comparing to that in groups C and D. There was also significant difference between groups C and D. Conclusion The releasing kinetics of P(DLLA-co-TMC)/FK506 microspheres matches the principle of nerve regeneration. It has remarkable effects on neuroregeneration, especially when it is locally administered earlier(within 24 hours).
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