Hamaishi Makoto, Orihashi Kazumasa, Isaka Mitsuhiro, Kumagai Hajime, Takahashi Shinya, Okada Kenji, Ohtaki Megu, Sueda Taijiro
Division of Clinical Medical Science, Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Ann Vasc Surg. 2009 Jan-Feb;23(1):128-35. doi: 10.1016/j.avsg.2008.05.010. Epub 2008 Aug 6.
Previous studies have indicated that high-dose intravenous edaravone (3-10mg/kg) protects against ischemic spinal cord injury. This study examined whether direct injection of low-dose edaravone into the clamped segment of the aorta prevents ischemic spinal cord injury. Spinal cord ischemia was induced in rabbits by aortic clamping below the renal artery and above the aortic bifurcation for 15min at normothermia. In groups A and B, 3 and 1mg/kg of edaravone, respectively, was injected into the clamped segment of the aorta immediately following aortic clamping. In group C, saline was injected. Neurological function was assessed at 8, 24, and 48hr and 7 days after reperfusion with Tarlov criteria. The spinal cord was histologically examined at 7 days with hematoxylin-eosin staining and in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. The Tarlov score remained grade 4 throughout the period in groups A and B, whereas it dropped to grade 0 or 1 at 7 days in group C, significantly higher in the former two groups. The number of intact motor neurons was significantly greater in groups A and B with less necrotic motor neurons than in group C. There was no significant difference in terms of spinal cord protection between groups A and B. There was no TUNEL-positive neuron in any group, indicating the absence of apoptosis. Low-dose intra-aortic edaravone injection prevents immediate neuronal injury by reducing neuronal cell damage in the early stage as well as delayed neuronal injury at 7 days.
先前的研究表明，高剂量静脉注射依达拉奉（3 - 10mg/kg）可预防缺血性脊髓损伤。本研究旨在探讨直接向夹闭的主动脉节段注射低剂量依达拉奉是否能预防缺血性脊髓损伤。通过在常温下将肾动脉下方和主动脉分叉上方的主动脉夹闭15分钟，诱导兔脊髓缺血。在A组和B组中，分别在主动脉夹闭后立即向夹闭的主动脉节段注射3mg/kg和1mg/kg的依达拉奉。在C组中，注射生理盐水。在再灌注后8小时、24小时、48小时和7天，根据塔尔洛夫标准评估神经功能。在7天时，对脊髓进行苏木精-伊红染色和原位末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）染色进行组织学检查。在整个观察期内，A组和B组的塔尔洛夫评分始终为4级，而C组在7天时降至0级或1级，前两组评分显著更高。A组和B组中完整运动神经元的数量明显多于C组，坏死运动神经元数量更少。A组和B组在脊髓保护方面无显著差异。任何组均未发现TUNEL阳性神经元，表明不存在细胞凋亡。主动脉内注射低剂量依达拉奉可通过减少早期神经元细胞损伤以及预防7天时的迟发性神经元损伤，预防即时神经元损伤。
