Delayed nerve repair is associated with diminished neuroenhancement by FK506
Delayed nerve repair is associated with diminished neuroenhancement by FK506
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DOI：
10.1097/00005537-200403000-00034
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发表时间：
2004-03-01
期刊：
影响因子：
2.6
通讯作者：
Mackinnon, SE
中科院分区：
文献类型：
--
作者：
Brenner, MJ;Fox, IK;Mackinnon, SE
目的/假设：免疫抑制剂FK506在许多研究中被证明可以促进神经再生，加速神经修复后的功能恢复。然而，在临床实践中，周围神经损伤患者的诊断和治疗往往被延误。本研究考察了当神经修复和FK506治疗延迟7天后，FK506是否仍能保持其神经再生特性。研究设计：体内实验室研究。方法：取32只Lewis大鼠行胫骨神经横断术，随机分为4个实验组：经FK506处理后立即修复组、未经FK506处理后立即修复组、经FK506处理后7 d延迟修复组、未经FK506处理后7 d延迟修复组。治疗动物每天皮下注射2mg /kg FK506。在神经修复后14、16和18天进行连续行走轨迹测量。修复后第18天，周围神经注射荧光示踪剂逆行标记。第21天，采集周围神经和脊髓，分别进行组织形态学分析和运动神经元细胞体计数。结果：FK506即刻修复组动物的纤维计数和神经百分比明显高于其他三组（P < 0.05），但早期功能恢复无统计学意义。其余三组的神经再生水平为中等水平，差异不显著。未给予FK506的延迟神经修复动物逆行运动神经元计数减少（P < 0.05）。结论：在大鼠胫骨神经横断模型中，FK506的神经再生作用在修复和开始FK506治疗延迟7天后明显减弱。
Objectives/Hypothesis: The immunosuppressive agent FK506 has been shown in many studies to enhance nerve regeneration and to accelerate functional recovery after immediate nerve repair. However, in clinical practice the diagnosis and treatment of patients with peripheral nerve injuries is often delayed. The study investigated whether FK506 would retain its neuroregenerative properties when nerve repair and initiation of FK506 therapy were delayed for 7 days. Study Design: In vivo laboratory study. Methods: Thirty-two Lewis rats underwent tibial nerve transection and were randomly assigned to four experimental groups: immediate repair with FK506 treatment, immediate repair without FK506 treatment, 7-day delayed repair with FK506 treatment, and 7-day delayed repair without FK506 treatment. Treated animals received daily subcutaneous injections of 2 mg/kg FK506. Serial walking track measurements were performed at 14,16, and 18 days after nerve repair. On day 18 after repair, peripheral nerves were injected with a fluorescent tracer for retrograde labeling. On day 21, peripheral nerves and spinal cords were harvested for histomorphometric analysis and motor neuron cell body counts, respectively. Results: Animals that underwent immediate repair with FK506 had significantly higher fiber counts and percentages of nerve than the other three groups (P < .05) but did not show statistically significant earlier functional recovery. The remaining three groups had intermediate levels of nerve regeneration that were not significantly different. Retrograde abled motor neurons counts were decreased in animals with delayed nerve repair that received no FK506 (P < .05). Conclusion: In a rat tibial nerve transection model, the neuroregenerative effects of FK506 diminished markedly when repair and initiation of FK506 therapy were delayed by 7 days.