Nafamostat mesilate attenuates neuronal damage in a rat model of transient focal cerebral ischemia through thrombin inhibition.

Nafamostat mesilate attenuates neuronal damage in a rat model of transient focal cerebral ischemia through thrombin inhibition.
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甲磺酸萘莫司他通过抑制凝血酶减轻短暂性局灶性脑缺血大鼠模型中的神经元损伤

DOI:
10.1038/srep05531
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发表时间:
2014-07-02
期刊:
影响因子:
4.6
通讯作者:
Liao H
Liao H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen T;Wang J;Li C;Zhang W;Zhang L;An L;Pang T;Shi X;Liao H

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有证据表明,凝血素是一种血液凝血蛋白,在这里介导了脑缺血中的神经元损伤,我们在这里测试了nafamostat resilate(一种丝氨酸蛋白抑制剂)的假设,可能会降低脑膜抑制作用的脑膜抑制作用。脑动脉2小时,然后22小时再灌注。在缺血期间的纳法摩氏症和灌注降低了脑梗塞的体积,凝血素体积和凝血酶的表达和活性El染色表明Nafamostat中脱酸盐缺血期间垂死的细胞数量减少。
Evidence suggests that thrombin, a blood coagulation serine protease, mediates neuronal injury in experimental cerebral ischemia. Here, we test the hypothesis that nafamostat mesilate, a serine protease inhibitor, may ameliorate ischemia-induced neuronal damage through thrombin inhibition after ischemic stroke. Focal ischemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery for 2 hours followed by 22 hours of reperfusion. The administration of nafamostat mesilate during ischemia and reperfusion reduced the brain infarct volume, edema volume and neurological deficit. Thrombin expression and activity in the ipsilateral striatum were increased after ischemia, whereas the administration of nafamostat mesilate significantly inhibited thrombin expression and activity. Immunostaining showed that the majority of thrombin was expressed in neurons. TUNEL staining showed that nafamostat mesilate reduced the number of dying cells during ischemia. A rat behavioral test showed that nafamostat mesilate treatment significantly improved the learning ability of ischemic rats. These results suggest that nafamostat mesilate may have a potential therapeutic role for neuroprotection against focal cerebral ischemia through thrombin inhibition.
DOI: 10.1038/35025229
发表时间: 2000-09-14
期刊: NATURE
影响因子: 64.8
作者:
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