Yazihan Nuray, Uzuner Kubilay, Salman Bulent, Vural Murat, Koken Tulay, Arslantas Ali
Ankara University, Faculty of Medicine, Molecular Biology Research and Development Unite, Ankara, Turkey.
Injury. 2008 Dec;39(12):1408-13. doi: 10.1016/j.injury.2008.03.010. Epub 2008 Jul 16.
Spinal cord injury (SCI) is a very destructive process for both patients and society. Lipid peroxidation is the main cause of the further secondary damage which starts after mechanical destruction of tissues. Recent studies have shown that erythropoietin (EPO) has neuroprotective properties. In this study, we aimed to see the effect of EPO treatment after spinal cord injury on the oxidant and anti-oxidant enzyme systems and the relationship with the N-methyl-D-Aspartate (NMDA) blockage. Spinal cord injury was produced by epidural compression with a cerebral vascular clip that has a closing force of 40 g for 30s after a limited multilevel laminectomy (T9-11). Experiment was done in 5 groups: Group 1: Sham-operated untraumatised, Group 2: SCI untreated, Group 3: 150 i.u./kg EPO injected i.p. at the end of the first hour following the trauma. Group 4: NMDA receptor antagonist ketamine (100mg/kg) i.p. Group 5: EPO+ketamine i.p. The experiments were finished after 12h of the trauma. The spinal cords were excised for biochemical examinations. Anti-oxidant enzymes; catalase and reduced glutathione (GSH) levels increased and lipid peroxidation product, malonyldialdehyde (MDA) level decreased in EPO treated group when compared to the other groups. TNF-alpha levels decreased in EPO treated group. Application of ketamine before EPO treatment decreased effects of EPO. In conclusion, our results suggest that 150 i.u./kg i.p. EPO, a therapeutic dose in anaemic patients, applied after 1h of spinal cord injury significantly attenuated the oxidative damage of spinal cord injuries in rats. This activity is abolished via ketamine pretreatment.
脊髓损伤（SCI）对患者和社会而言都是极具破坏性的过程。脂质过氧化是组织受到机械性损伤后引发进一步继发性损伤的主要原因。近期研究表明，促红细胞生成素（EPO）具有神经保护特性。在本研究中，我们旨在观察脊髓损伤后EPO治疗对氧化酶和抗氧化酶系统的影响以及与N-甲基-D-天冬氨酸（NMDA）阻断的关系。在进行有限的多节段椎板切除术（T9 - 11）后，用闭合力为40克的脑血管夹进行30秒的硬膜外压迫以造成脊髓损伤。实验分为5组：第1组：假手术未受伤组；第2组：未治疗的脊髓损伤组；第3组：在创伤后第一小时末腹腔注射150国际单位/千克EPO；第4组：腹腔注射NMDA受体拮抗剂氯胺酮（100毫克/千克）；第5组：腹腔注射EPO + 氯胺酮。创伤12小时后结束实验。取出脊髓进行生化检查。与其他组相比，EPO治疗组的抗氧化酶（过氧化氢酶和还原型谷胱甘肽（GSH））水平升高，脂质过氧化产物丙二醛（MDA）水平降低。EPO治疗组的肿瘤坏死因子-α（TNF-α）水平降低。在EPO治疗前应用氯胺酮会降低EPO的效果。总之，我们的结果表明，脊髓损伤1小时后腹腔注射150国际单位/千克EPO（贫血患者的治疗剂量）可显著减轻大鼠脊髓损伤的氧化损伤。氯胺酮预处理可消除这种活性。
