利用神经再生室观察FK506促进神经再生的实验研究

目的探讨免疫抑制剂FK506促神经再生的作用及药物应用方法。方法将雄性SD大鼠60只随机分成3组,每组20只,切断双侧坐骨神经制成坐骨神经再生室模型。A组在再生室内注入生理盐水;B组在再生室内注入盐水,颈后皮下注射FK5061mg／kg,连续14d;C组在再生室内注入1μg／mlFK506。观察神经损伤局部的免疫反应、检测腓肠肌湿重、组织形态学及图像分析、电生理学。结果B、C组大鼠神经损伤局部淋巴细胞浸润程度较A组轻微。6周时大鼠腓肠肌湿重为：A组平均579mg,B组平均725mg,C组平均761mg,B、C组大鼠腓肠肌湿重明显优于A组;组织形态学观察与图像分析显示,有髓神经纤维总数为：A组平均720根,B组平均778根,C组平均772根,在有髓神经纤维密度、平均轴突直径、髓鞘厚度等指标中,B组结果明显优于A组。结论（1）大鼠全身应用FK506后具有神经保护和神经营养作用,可加快神经功能的恢复。（2）局部应用FK506对早期损伤神经有一定的保护作用。

Effect of FK506 on axonal regeneration of rat sciatic nerve in regeneration chamber: an experimental study

OBJECTIVE: To evaluate the effect of FK506 on expediting nerve regeneration of rat Sciatic Nerve in regeneration chamber and to look for a proper way of its administration to treat peripheral nerve injuries. METHODS: Sixty adult male SD rats which were randamizely divided into 3 groups received a neurotomy to bilateral sciatic nerves, then we reconnected the broken nerves with silicon tube to make regeneration chambers. The regeneration chambers were filled with either normal saline (group A and group B) or 1 microg/ml FK506 (group C). The rats of group B also received daily injection of FK506 (1 mg/kg) at the back of the neck for 14 days. Local immunoreaction, weight of fresh gastrocnemius muscles, histological changes and electrophysiology were observed at designate time after neurotomy. RESULTS: At 6 weeks postoperation the extent of local lymphocytes infiltration in group B and C were less than that in group A, all results in group B were much better than that of group A. Results of group C were better than that of group A without significance. CONCLUSIONS: (1) Systemic administration of FK506 (1 mg/kg) showed neuroprotective and neurotrophic effect, which can facilitate nerve regeneration and promote functional recovery. (2) Local administration of FK506 (1 microg/ml) showed some extent of neuroprotective effect at early period of nerve injury, but the neurotrophic function is uncertain and still needs to be studied further.