Protective effect of endothelin type A receptor antagonist on brain edema and injury after transient middle cerebral artery occlusion in rats
Protective effect of endothelin type A receptor antagonist on brain edema and injury after transient middle cerebral artery occlusion in rats
复制标题
DOI：
10.1161/hs0901.94259
复制
发表时间：
2001-09-01
期刊：
影响因子：
8.3
通讯作者：
Fujimoto, M
中科院分区：
文献类型：
--
作者：
Matsuo, Y;Mihara, S;Fujimoto, M
背景和目的：最近的证据有力地表明内皮素（endothelins，ET）在血脑屏障（blood-brain barrier，BBB）功能的调节中起重要作用。本研究的目的是评价脑缺血再灌注后脑水肿形成和血脑屏障通透性变化中ET-1的作用。方法我们检测了脑组织ET-1含量，并评价了特异性ET A型受体（ETA）拮抗剂S-0139对脑水肿形成、梗死发展、结果大脑中动脉闭塞（MCAO）后再灌注1小时，脑内ET-1含量在缺血前3小时无明显变化，6小时开始升高，48小时后几乎持续升高。在再灌注期间输注S-0139（0.03 - 1.0 mg/kg/h）的大鼠显示出再灌注后24小时脑含水量增加的剂量依赖性和显著衰减。再灌注10分钟和1小时后开始输注S-0139时，脑水肿形成和梗死范围明显减轻。此外，S-0139后处理显着减弱了埃文斯蓝染料定量白蛋白渗出的增加，并改善了脑缺血/再灌注后动物的死亡率。结论-我们的数据表明，输注S-0139（一种ETA拮抗剂）导致短暂MCAO后脑损伤和血浆渗出显着减少。因此，ETAS可能至少部分通过增加BBB通透性而导致脑缺血/再灌注损伤。
Background and Purpose-Recent evidence strongly suggests that endothelins (ETs) play an important role in the regulation of blood-brain barrier (BBB) functions. The aim of the present study was to evaluate the role of ETs on edema formation and BBB permeability change after cerebral ischemia/reperfusion.Methods-We examined the brain tissue ET-1 content and evaluated the time and dose response of the therapeutic effects of the specific ET type A receptor (ETA) antagonist, S-0139, on brain edema formation, development of infarction, and disruption of BBB after I hour of middle cerebral artery occlusion (MCAO) in rats.Results-After 1-hour MCAO and reperfusion, the brain ET-1 content did not change during the first 3 hours, increased at 6 hours, and rose almost continuously over 48 hours in the ischemic region as well as in the ischemic rim. Rats infused with S-0139 (0.03 to 1.0 mg/kg per hour) during reperfusion showed dose-dependent and significant attenuation of the increase in brain water content 24 hours after reperfusion. When the infusion of S-0139 was begun after 10 minutes and 1 hour of reperfusion, the brain edema formation and infarct size were significantly attenuated. Furthermore, posttreatment with S-0139 significantly attenuated the increased Evans blue dye-quantified albumin extravasation and improved the mortality of animals after cerebral ischemia/reperfusion.Conclusions-Our data demonstrate that infusion with S-0139, an ETA antagonist, results in significant reduction of brain injury and plasma extravasation after transient MCAO. Thus, ETs may contribute to cerebral ischemia/reperfusion injury at least partly by increasing the BBB permeability via ETAS.