Yamashita Tsutomu, Sato Takumi, Sakamoto Kumi, Ishii Hiromitsu, Yamamoto Junichiro
Laboratory of Medical Technology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan.
Laboratory of Medical Technology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan.
Thromb Res. 2015 Jun;135(6):1209-13. doi: 10.1016/j.thromres.2015.04.011. Epub 2015 Apr 14.
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.
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.
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.
These results support the hypothesis that edaravone accelerates thrombolysis by alteplase.
溶栓治疗后的再灌注损伤可产生不良神经学效应。自由基清除剂依达拉奉与重组组织型纤溶酶原激活剂阿替普酶联合用于治疗急性缺血性卒中。然而，这种联合使用的基础研究仍不充分。在此，我们使用体内模型研究依达拉奉对阿替普酶诱导溶栓的影响。
通过使用大鼠肠系膜微血管中氦氖激光诱导血栓形成模型评估溶栓情况。使用图像分析软件Image-Pro Plus（美国Media Cybernetics公司）分析血栓体积变化。有三个实验组（安慰剂组、阿替普酶0.6mg/kg组、阿替普酶0.6mg/kg +依达拉奉10.5mg/kg组）。采用我们之前使用的相对光密度法比较血栓体积的序贯变化（0至60分钟）。
在安慰剂组中，反映溶栓程度的60分钟时血栓体积为初始值的97.2%±5.7%。在阿替普酶组中，20分钟后血栓体积降至70.7%±4.1%（P<0.01），60分钟后降至14.2%±6.6%。在阿替普酶+依达拉奉组中，10分钟后血栓体积降至66.9%±7.2%（P<0.001），60分钟后降至10.9%±2.3%。
这些结果支持依达拉奉可加速阿替普酶溶栓这一假说。
