FK506 reduces tissue damage and prevents functional deficit after spinal cord injury in the rat
FK506 reduces tissue damage and prevents functional deficit after spinal cord injury in the rat
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DOI：
10.1002/jnr.20605
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发表时间：
2005-09-15
影响因子：
4.2
通讯作者：
Verdú, E
中科院分区：
文献类型：
--
作者：
López-Vales, R;García-Alías, G;Verdú, E
与甲基强的松龙（methylprednisolone， MP）治疗相比，我们检测了FK506在减少脊髓损伤后组织损伤方面的疗效。将大鼠置于光化学损伤（T8）后，给予MP （30mg /kg）、FK506 （2mg /kg）或生理盐水。另一组初始注射FK506 (2mg /kg)，随后每日注射（0.2 mg/kg腹腔注射）。术后14天，通过开场行走、斜面试验、运动诱发电位（MEPs）和h反射反应评估功能恢复情况。测定损伤脊髓组织保留、胶质原纤维酸性蛋白（GFAP）、生物素化番茄凝集素LEC、环氧合酶-2 （COX-2）、诱导型一氧化氮合酶（NOS）和白细胞介素1 β (IL-1 β)免疫反应性。与盐水处理的大鼠相比，fk506处理的动物表现出明显更好的神经系统预后，更高的MEP振幅和更低的h波振幅。相反，给药MID与盐水处理组没有显著差异。组织学检查显示，与生理盐水和mp处理的动物相比，fk506处理的组织保留最大。与给予MP或生理盐水的动物相比，给予FK506的动物GFAP和COX-2反应性降低，而在FK506和MP处理组中，IL-1 β的表达也同样降低。FK506和mp注射动物在3 dpo时的小胶质细胞/巨噬细胞反应降低，但仅在mp治疗动物在7 dpo时与盐水注射大鼠相比。反复服用FK506比单次服用FK506更能改善功能和组织学结果。结果表明，FK506对脊髓损伤具有保护作用，可作为治疗脊髓损伤的潜在药物。(c) 2005 Wiley-Liss, Inc。
We examined the efficacy of FK506 in reducing tissue damage after spinal cord injury in comparison to methylprednisolone (MP) treatment. Rats were subjected to a photochemical injury (T8) and were given a bolus of MP (30 mg/kg), FK506 (2 mg/kg), or saline. An additional group received an initial bolus of FK506 (2 mg/kg) followed by daily injections (0.2 mg/kg intraperitoneally). Functional recovery was evaluated using open-field walking, inclined plane tests, motor evoked potentials (MEPs), and the H-reflex response during 14 days post-operation (dpo). Tissue sparing and glial fibrillary acidic protein (GFAP), biotinylated tomato lectin LEC, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (NOS), and interleukin 1 beta (IL-1 beta) immunoreactivity were quantified in the injured spinal cord. FK506-treated animals demonstrated significantly better neurologic outcome, higher MEP amplitudes, and lower H-wave amplitude compared to that of saline-treated rats. In contrast, administration of MID did not result in significant differences with respect to the saline-treated group. Histologic examination revealed that tissue sparing was largest in FK506-treated compared to saline and MP-treated animals. GFAP and COX-2 reactivity was decreased in animals treated with FK506 compared to that in animals given MP or saline, whereas IL-1 beta expression was similarly reduced in both FK506-and MP-treated groups. Microglia/macrophage response was reduced in FK506 and MP-injected animals at 3 dpo, but only in MP-treated animals at 7 dpo with respect to saline-injected rats. Repeated administrations of FK506 improved functional and histologic results to a greater degree than did a single bolus of FK506. The results indicate that FK506 administration protects the damaged spinal cord and should be considered as potential therapy for treating spinal cord injuries. (c) 2005 Wiley-Liss, Inc.