Zhao Jia, Zheng Xifu, Fu Chongyang, Qu Wei, Wei Guoqiang, Zhang Weiguo
Department of Orthopedic Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116011, China; DaLian the Sixth People's Hospital, Dalian 116031, China.
Department of Orthopedic Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
J Neurol Sci. 2014 Sep 15;344(1-2):20-6. doi: 10.1016/j.jns.2014.06.005. Epub 2014 Jun 12.
FK506 has been shown to exert neurotrophic and neuroprotective effects, but its long-term application for nerve regeneration is limited. This study evaluated the potential application of a novel FK506-loaded chitosan conduit for peripheral nerve repair, and explored the underlying mechanism. A sciatic nerve injury model was created in male Wistar rats, which were then randomly divided into three treatment groups (n=40, each): chitosan-only, chitosan+FK506 injection, and FK506-loaded chitosan. We found significant recovery of normal morphology of sciatic nerves and higher density of myelinated nerve fibers in rats treated with FK506-loaded chitosan. Similarly, the total number of myelinated nerve fibers, myelin sheath thickness, and axon diameters were significantly higher in this group compared with the others, and the compound muscle action potentials and motor nerve conduction velocity values of sciatic nerves were significantly higher. BDNF and TrkB levels in motor neurons were highest in rats treated with FK506-loaded chitosan. In conclusion, FK506-loaded chitosan promoted peripheral nerve repair and regeneration in a rat model of sciatic nerve injury. These effects are correlated with increased BDNF and TrkB expression in motor neurons.
已证明FK506具有神经营养和神经保护作用,但其在神经再生方面的长期应用受到限制。本研究评估了一种新型载有FK506的壳聚糖导管在周围神经修复中的潜在应用,并探讨了其潜在机制。在雄性Wistar大鼠中建立坐骨神经损伤模型,然后将其随机分为三个治疗组(每组n = 40):仅壳聚糖组、壳聚糖+FK506注射组和载有FK506的壳聚糖组。我们发现,接受载有FK506的壳聚糖治疗的大鼠坐骨神经正常形态有显著恢复,有髓神经纤维密度更高。同样,该组有髓神经纤维总数、髓鞘厚度和轴突直径均显著高于其他组,坐骨神经的复合肌肉动作电位和运动神经传导速度值也显著更高。接受载有FK506的壳聚糖治疗的大鼠运动神经元中的BDNF和TrkB水平最高。总之,载有FK506的壳聚糖促进了坐骨神经损伤大鼠模型的周围神经修复和再生。这些作用与运动神经元中BDNF和TrkB表达增加相关。