Local low dose curcumin treatment improves functional recovery and remyelination in a rat model of sciatic nerve crush through inhibition of oxidative stress
Local low dose curcumin treatment improves functional recovery and remyelination in a rat model of sciatic nerve crush through inhibition of oxidative stress
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DOI：
10.1016/j.neuropharm.2018.07.001
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发表时间：
2018-09-01
影响因子：
4.7
通讯作者：
Billet, Fabrice
中科院分区：
文献类型：
--
作者：
Caillaud, Martial;Chantemargue, Benjamin;Billet, Fabrice
周围神经的创伤性损伤是常见的，然而，目前缺乏具体的药物治疗。姜黄素具有抗氧化，抗炎和神经保护特性，但治疗用途需要高口服剂量，特别是由于其生物利用度低。本研究的目的是调查使用低剂量姜黄素的局部和持续治疗对大鼠坐骨神经挤压（SNC）后功能恢复和神经再生的影响。姜黄素通过渗透泵给药，并在损伤部位用导管输送药物（0.2 mg/天，持续4周）。在功能上，在姜黄素治疗的动物中观察到机械灵敏度、受伤爪的手指间距、熟练行走和握力的早期改善。姜黄素治疗增加了致密髓鞘蛋白（MPZ和PMP 22）的表达，髓鞘厚度，并相应地增加了运动和敏感神经传导速度。腓肠肌的显微镜分析表明姜黄素诱导的神经源性病变减少。姜黄素治疗减少了活性氧（ROS）（这是显着产生的巨噬细胞），脂质过氧化和转录因子Nrf 2的表达增加的生产。计算机模拟分析表明，姜黄素结合了在生物膜中心成为有效的脂质过氧化抑制剂所需的所有特性，从而保护它们因ROS而降解。这种抗氧化能力可能有助于SNC损伤后姜黄素的有益作用。这些结果表明，当局部给药时，低剂量的姜黄素代表了外周神经再生的有希望的疗法。(C)2018爱思唯尔有限公司版权所有
Traumatic injuries to peripheral nerves are frequent, however, specific pharmacological treatments are currently lacking. Curcumin has antioxidant, anti-inflammatory and neuroprotective properties but high oral doses are required for therapeutic use, particularly due to its low bioavailability. The aim of the present study was to investigate the effects of local and continuous treatment using low curcumin doses on functional recovery and nerve regeneration after rat sciatic nerve crush (SNC). Curcumin was administered by osmotic pumps with a catheter delivering the drug at the injury site (0.2 mgiday for 4 weeks). Functionally, early improvements in mechanical sensitivity, finger spacing of the injured paw, skilful walking and grip strength were observed in curcumin-treated animals. The curcumin treatment increased expression of compact myelin proteins (MPZ and PMP22), myelin sheath thickness and, correspondingly, increased motor and sensitive nerve conduction velocity. Microscopic analysis of gastrocnemius muscle indicated a curcumin-induced decrease in neurogenic lesions. Curcumin treatment reduced the production of reactive oxygen species (ROS) (which were notably produced by macrophages), lipid peroxidation and increased expression of transcription factor Nrf2. In silico analyses indicated that curcumin combines all the characteristics required to be an efficient lipid peroxidation inhibitor at the heart of biological membranes, hence protecting their degradation due to ROS. This antioxidant capacity is likely to contribute to the beneficial effects of curcumin after SNC injury. These results demonstrate that, when administrated locally, low doses of curcumin represent a promising therapy for peripheral nerve regeneration. (C) 2018 Elsevier Ltd. All rights reserved.