Neuroprotective effects of high-dose vs low-dose melatonin after blunt sciatic nerve injury
Neuroprotective effects of high-dose vs low-dose melatonin after blunt sciatic nerve injury
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DOI：
10.1007/s00381-007-0366-x
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发表时间：
2008-01-01
影响因子：
1.4
通讯作者：
Oakes, W. Jerry
中科院分区：
文献类型：
--
作者：
Shokouhi, Ghaffar;Tubbs, R. Shane;Oakes, W. Jerry
介绍褪黑激素，松果体的分泌产物，具有强大的抗氧化性能。本研究的目的是比较低剂量（10 mg/kg）和高剂量（50 mg/kg）褪黑素对实验性钝性坐骨神经损伤（SNI）早期脂质过氧化水平和超微结构变化的影响。我们相信这是第一个研究，以评估剂量依赖性的褪黑激素的神经保护作用后，钝性周围nerveinjure.Materials和方法大鼠随机分为5组，每组10只动物。仅SNI大鼠经历神经损伤程序。SNI+溶媒组接受SNI和腹膜内注射溶媒（稀释乙醇）作为安慰剂。SNI+低剂量或高剂量褪黑素组分别腹腔注射褪黑素10 mg/kg或50 mg/kg。对照组无手术、褪黑激素或溶媒注射。SNI是通过在股方肌上缘夹持坐骨神经2 min诱导的。结果坐骨神经损伤后6 h取材，进行生化和超微结构分析。创伤使坐骨神经的脂质过氧化反应增加3.6倍（SNI组为153.85 ± 18.73，对照组为41.73 ± 2.23，P < 0.01）。低（p=0.02）和高褪黑激素组神经脂质过氧化反应分别降低25%和57.25%（P < 0.01）（高剂量组65.76 +/-2.47 vs低剂量褪黑激素组115.08 +/-7.03）.讨论虽然低剂量褪黑激素减少了坐骨神经中创伤诱导的髓鞘破坏和轴突变化，结论褪黑素对钝性创伤后周围神经纤维的脂质过氧化损伤具有明显的保护作用，尤其是50 mg/kg剂量的褪黑素，对钝性创伤后周围神经纤维的脂质过氧化损伤具有保护作用。通过进一步的研究，我们希望这些数据可以证明对治疗神经损伤患者的临床医生有用。
Introduction Melatonin, the secretory product of the pineal gland, has potent antioxidant properties. The aim of this study was to compare the effects of low-dose (10 mg/kg) vs high-dose (50 mg/kg) melatonin on early lipid peroxidation levels and ultrastructural changes in experimental blunt sciatic nerve injury (SNI). We believe this to be the first study to assess the dose-dependent neuroprotective effects of melatonin after a blunt peripheral nerve injury.Materials and methods Rats were randomly allocated into 5 groups of 10 animals each. The SNI only rats underwent a nerve injury procedure. The SNI plus vehicle group received SNI and intraperitoneal injection of vehicle (diluted ethanol) as a placebo. The SNI plus low-dose or high-dose melatonin groups received intraperitoneal melatonin at doses of 10 mg/kg or 50 mg/kg, respectively. Controls had no operation, melatonin or vehicle injection. SNI was induced by clamping the sciatic nerve at the upper border of the quadratus femoris for 2 min.Results Sciatic nerve samples were harvested 6 h after nerve injury and processed for biochemical and ultrastructural analysis. Trauma increased the lipid peroxidation of the sciatic nerve by 3.6-fold (153.85 +/- 18.73 in SNI only vs 41.73 +/- 2.23 in control rats, P < 0.01). Low (p=0.02) and high (p < 0.01) doses of melatonin attenuated the nerve lipid peroxidation by 25% and 57.25%, respectively (65.76 +/- 2.47 in high-dose vs 115.08 +/- 7.03 in low-dose melatonin groups).Discussion Although low-dose melatonin reduced trauma-induced myelin breakdown and axonal changes in the sciatic nerve, high-dose melatonin almost entirely neutralized any ultrastructural changes.Conclusion Our results suggest that melatonin, especially at a dose of 50 mg/kg, has a potent neuroprotective effect and can preserve peripheral neural fibers from lipid peroxidative damage after blunt trauma. With further investigations, we hope that these data may prove useful to clinicians who treat patients with nerve injuries.