1st Neurosurgery Clinic, Ministry of Health, Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey.
Acta Neurochir (Wien). 2012 Jun;154(6):1037-43; discussion 1043-4. doi: 10.1007/s00701-012-1298-0. Epub 2012 Feb 22.
Darbepoetin-alpha (DA) is a novel erythropoiesis-stimulating agent developed for treating anemia. In animal models, recombinant human erythropoietin has been reported to be beneficial for neuroprotection. In this study, we determined whether DA would protect the spinal cord against ischemia-reperfusion injury in a rabbit model.
Forty rabbits were randomized into five groups of eight animals each: group 1 (sham), group 2 (ischemia), group 3 (vehicle), group 4 (30 mg/kg methylprednisolone), group 5 (30 μg/kg DA). Only laparotomy was performed in the sham group. In all the other groups, the spinal cord ischemia model was created by a 20-min occlusion of the aorta just caudal to renal artery with an aneurysm clip. The drugs were administered immediately after the clamp was removed. The animals were killed 24 h later. Spinal cord segments between L2 and L5 were harvested for analysis. Neurological evaluation was performed with the Tarlov scoring system just before the animals were killed. Level of tissue malondialdehyde was analyzed as a marker of lipid peroxidation and tissue caspase-3 activity as a marker of apoptosis. Also, histopathological evaluation of the tissues was performed.
Both malondialdehyde and caspase-3 levels were significantly decreased by DA administration. Histopathological evaluation of the tissues also demonstrated decrease in neuronal degeneration and infiltration parameters after DA administration. In the DA group, neurological outcome scores were statistically significantly better compared with the ischemia and the vehicle groups.
Although further studies considering different dose regimens and time intervals are required, DA was shown to be at least as effective as methylprednisolone in spinal cord ischemia/reperfusion model.
达贝泊汀-α（DA）是一种新型的红细胞生成素刺激剂，用于治疗贫血。在动物模型中，重组人红细胞生成素已被报道对神经保护有益。在这项研究中，我们确定了 DA 是否会在兔模型中保护脊髓免受缺血再灌注损伤。
40 只兔子随机分为五组，每组 8 只：第 1 组（假手术）、第 2 组（缺血）、第 3 组（载体）、第 4 组（30mg/kg 甲基强的松龙）、第 5 组（30μg/kg DA）。仅在假手术组进行剖腹手术。在所有其他组中，通过用动脉瘤夹夹闭肾动脉下方的主动脉 20 分钟来创建脊髓缺血模型。夹闭去除后立即给予药物。24 小时后处死动物。采集 L2 至 L5 之间的脊髓段进行分析。在处死动物之前，使用 Tarlov 评分系统进行神经学评估。分析组织丙二醛水平作为脂质过氧化的标志物，组织 caspase-3 活性作为细胞凋亡的标志物。还对组织进行了组织病理学评估。
DA 给药可显著降低丙二醛和 caspase-3 水平。DA 给药后组织的组织病理学评估也表明神经元变性和浸润参数减少。在 DA 组，神经功能评分与缺血组和载体组相比具有统计学意义上的显著改善。
尽管需要进一步研究考虑不同的剂量方案和时间间隔，但 DA 在脊髓缺血再灌注模型中至少与甲基强的松龙一样有效。
