Department of Cardiovascular Surgery, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
J Vasc Surg. 2010 Feb;51(2):445-52. doi: 10.1016/j.jvs.2009.10.081.
Paraplegia remains a serious complication after surgical repair of thoracoabdominal aortic aneurysms. The aim of this study was to evaluate the neuroprotective efficacy of fasudil, a Rho kinase (ROCK) inhibitor, by reducing the number of infiltrating cells in the ventral horn and increasing the induction of eNOS against ischemic spinal cord injury in rabbits.
Eighteen Japanese white rabbits were divided into three groups: saline (group 1, n = 7, 4 degrees C) and fasudil (group 2, n = 6, 4 degrees C) were immediately infused into the isolated segmental lumbar arteries over 30 seconds after aortic clamping. Group 3 (n = 5) was the sham-operated group. Hind limb function was evaluated 4 and 8 hours, and 1 and 2 days after 15 minutes of transient ischemia. Cell damage was analyzed by hematoxylin and eosin staining and temporal profiles of endothelial nitric oxide synthase immunoreactivity were performed. The number of intact motor neuron cells and infiltrating cells in the ventral horn were compared.
Two days after reperfusion, group 2 and group 3 showed better neurologic function, a greater number of intact motor neuron cells, and a smaller number of infiltrating cells in the ventral horn than group 1. The induction of endothelial nitric oxide synthase (eNOS) was prolonged up to 2 days after reperfusion in group 2.
These results indicate that fasudil has neuroprotective effects against ischemic spinal cord injury in rabbits by reducing the number of infiltrating cells in the ventral horn and prolonging the expression of eNOS.
截瘫仍然是胸主动脉瘤手术后的严重并发症。本研究旨在评估 Rho 激酶（ROCK）抑制剂法舒地尔通过减少腹侧角浸润细胞的数量和增加诱导内皮型一氧化氮合酶（eNOS）对兔缺血性脊髓损伤的神经保护作用。
18 只日本白兔分为三组：生理盐水组（1 组，n = 7，4°C）和法舒地尔组（2 组，n = 6，4°C），在主动脉夹闭后 30 秒内立即将药物注入隔离的节段性腰动脉。第 3 组（n = 5）为假手术组。在缺血 15 分钟后 4、8 小时和 1、2 天评估后肢功能。通过苏木精和伊红染色分析细胞损伤，并进行内皮型一氧化氮合酶免疫反应的时间过程分析。比较完整运动神经元细胞的数量和腹侧角的浸润细胞。
再灌注后 2 天，2 组和 3 组的神经功能明显优于 1 组，完整运动神经元细胞数量较多，腹侧角浸润细胞数量较少。内皮型一氧化氮合酶（eNOS）的诱导在 2 天内持续增加。
这些结果表明，法舒地尔通过减少腹侧角浸润细胞的数量和延长 eNOS 的表达，对兔缺血性脊髓损伤具有神经保护作用。
