The free-radical scavenger edaravone accelerates thrombolysis with alteplase in an experimental thrombosis model
The free-radical scavenger edaravone accelerates thrombolysis with alteplase in an experimental thrombosis model
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DOI：
10.1016/j.thromres.2015.04.011
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发表时间：
2015-06-01
影响因子：
7.5
通讯作者：
Yamamoto, Junichiro
中科院分区：
文献类型：
--
作者：
Yamashita, Tsutomu;Sato, Takumi;Yamamoto, Junichiro
背景与目的：溶栓治疗后的再灌注损伤可对神经系统产生不良影响。自由基清除剂依达拉奉联合重组组织型纤溶酶原激活剂阿替普酶治疗急性缺血性卒中。然而，对这种组合使用的基本调查仍然不足。在这里，我们使用体内模型来研究依达拉奉对阿替普酶诱导的溶栓的影响。方法：采用氦氖激光诱导大鼠肠系膜微血管血栓形成模型，观察其溶栓情况。使用图像分析软件image - pro Plus （Media Cybernetics， USA）分析血栓体积的变化。实验组分为安慰剂组、阿替普酶0.6 mg/kg组、阿替普酶0.6 mg/kg组+依达拉奉10.5 mg/kg组。使用我们之前使用的相对光密度方法比较血栓体积的顺序变化（0至60分钟）。结果：安慰剂组60min时血栓体积为初始值的97.2% +/- 5.7%，反映溶栓程度。阿替普酶组血栓体积在20min后降至70.7% +/- 4.1% (P < 0.01)， 60min后降至14.2% +/- 6.6% （P < 0.01）。阿替普酶+依达拉奉组血栓体积在10min后降至66.9% +/- 7.2% (P < 0.001)， 60min后降至10.9% +/- 2.3% （P < 0.001）。结论：这些结果支持依达拉奉加速阿替普酶溶栓的假设。(C) 2015 Elsevier Ltd.版权所有。
Background and Purpose: Reperfusion injury after thrombolytic therapy can have adverse neurologic effects. The free-radical scavenger edaravone is used in combination with the recombinant tissue plasminogen activator alteplase to treat acute ischemic stroke. However, basic investigations of this combination use remain inadequate. Here, we used an in vivo model to investigate the effects of edaravone on alteplase-induced thrombolysis.Methods: Thrombolysis was evaluated by using a He-Ne-laser-induced thrombosis model in rat mesenteric microvessels. Changes in thrombus volume were analyzed with the image analysis software Image-Pro Plus (Media Cybernetics, USA). There were three experimental groups (placebo, alteplase 0.6 mg/kg, alteplase 0.6 mg/kg + edaravone 10.5 mg/kg). Sequential changes (0 to 60 min) in thrombus volume were compared by using a relative optical density method that we had used previously.Results: In the placebo group, the thrombus volume at 60 min, reflecting the extent of thrombolysis, was 97.2% +/- 5.7% of the initial value. In the alteplase group, thrombus volume decreased to 70.7% +/- 4.1% (P < 0.01) after 20 min and 14.2% +/- 6.6% after 60 min. In the alteplase + edaravone group, thrombus volume decreased to 66.9% +/- 7.2% (P < 0.001) after 10 min and 10.9% +/- 2.3% after 60 min.Conclusions: These results support the hypothesis that edaravone accelerates thrombolysis by alteplase. (C) 2015 Elsevier Ltd. All rights reserved.