Neutrophil elastase inhibitor prevents ischemic brain damage via reduction of vasogenic edema
Neutrophil elastase inhibitor prevents ischemic brain damage via reduction of vasogenic edema
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DOI：
10.1038/hr.2010.58
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发表时间：
2010-07-01
影响因子：
5.4
通讯作者：
Iwama, Toru
中科院分区：
文献类型：
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作者：
Ikegame, Yuka;Yamashita, Kentaro;Iwama, Toru
中性粒细胞弹性蛋白酶的释放是急性脑缺血时的有害炎症反应之一。因此，抑制中性粒细胞释放的弹性蛋白酶可能是治疗急性中风的有效策略。为了验证这一假设，我们在小鼠局灶性缺血模型中检测了选择性中性粒细胞弹性酶抑制剂西维司他的作用。结果表明，西司他可减少脑水肿和血管通透性，从而改善急性局灶性缺血的神经功能缺损。通过鉴定血管内皮细胞来分析微血管的结构，将荧光素标记的格里菲斯草凝集素i -分离素B4注射到尾静脉中进行预标记。对照组梗死区微血管大部分结构破坏。与之形成鲜明对比的是，西韦斯利特治疗组的边界区微血管得到了很好的维持。此外，西韦司他组缺血边缘血管生成素-1的表达升高。此外，中性粒细胞弹性酶抑制剂可使培养的人脑微血管内皮细胞免受中性粒细胞弹性酶诱导的损伤。上述结果提示，抑制中性粒细胞弹性蛋白酶可能通过提高血管生成素-1的表达和内皮细胞的存活来保护急性脑缺血血脑屏障功能。高血压研究（2010）33,703-707；doi: 10.1038 / hr.2010.58;2010年5月20日在线发布
Release of neutrophil elastase is one of the harmful inflammatory reactions in acute cerebral ischemia. Therefore, inhibition of elastase released from neutrophils could be a useful strategy for the treatment of acute stroke. To evaluate this hypothesis, the effect of sivelestat, a selective neutrophil elastase inhibitor was examined in a mouse model of focal ischemia. The results obtained indicate that sivelestat reduced brain edema and vascular permeability, and subsequently improved the neurological deficit in an acute focal ischemia. The architecture of microvessels was analyzed by identifying vascular endothelial cells, which were prelabeled by injecting fluorescein-labeled Griffonia simplicifolia lectin I-isolectin B4 into a tail vein. Most of the microvessels in the infarcted area were structurally destroyed in the control group. In sharp contrast, microvessels in the boundary zone were well maintained in the sivelestat-treated group. Moreover, the expression of angiopoietin-1 was elevated at the ischemic margin in the sivelestat-treated group. Furthermore, the neutrophil elastase inhibitor rescued human brain microvascular endothelial cells in culture from neutrophil elastase-induced damage. These results suggest that neutrophil elastase inhibition could protect blood-brain barrier function in acute cerebral ischemia by augmentation of angiopoietin-1 expression and survival of endothelial cells. Hypertension Research (2010) 33, 703-707; doi: 10.1038/hr.2010.58; published online 20 May 2010