Analysis of the microcirculatory disturbance in cerebral ischemia

脑缺血微循环障碍分析

• 批准号: 05671160
• 负责人: YOSHIMINE Toshiki
• 金额: $ 1.34万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671160/
• 关键词: Cerebral ischemia; Microcirculation; Free radical; Leukocyte; Superoxide; SOD; Nitric oxide; cerebral ischemia; microcirculation; free radical; chemiluminescence; superoxide; nitric oxide

This study presented the following three important informations on the pathophysiology and treatment of the microcirculatory disturbances in cerebral ischemia.1) Production of nitric oxide (NO) in focal cerebral ischemia.The levels of nitrate (NO_3) and nitrite (NO_2) in the jugular venous blood in rat focal cerebral ischemia were determined by Griess reaction. The results demonstrated the levels of NO_3^- were significantly increased at 2 hours of ischemia and at 30min reperfusion after 2 hours of ischemia. This increase in NO_3^- was blocked by N^G-nitro-L-arginine (L-NAME,20mg/kg).2)Improvement of microcirculation with SOD.The administration of recombinant human Cu, Zn-superoxide dismutase increased the length of plasma-perfused microvessels as was analyzed at 3 hours after occlusion of the middle cerebral artery in rats.3)Leukocytes as a source of free radicals in ischemic brain.Peripheral leukocytopenia (1,180/mm^3) was induced by cyclophosphamide in rats. The chemiluminescence of the slices of the ischemic hemispheres obtained at 3 hours of middle cerebral artery occlusion in those rats was significantly reduced as compared to that of normal leukocyte count (5,180/mm^3).

本研究对脑缺血微循环障碍的病理生理学和治疗提供了以下三个重要信息。1）局灶性脑缺血中一氧化氮（NO）的产生。颈静脉中硝酸盐（NO_3）和亚硝酸盐（NO_2）的水平采用格里斯反应测定大鼠局灶性脑缺血的静脉血。结果表明，NO_3^-水平在缺血2小时和缺血2小时后再灌注30分钟时显着升高。 NO_3^-的这种增加被N^G-硝基-L-精氨酸（L-NAME，20mg/kg）阻断。2）用SOD改善微循环。重组人铜、锌超氧化物歧化酶的施用增加了长度大鼠大脑中动脉闭塞后 3 小时对血浆灌注的微血管进行分析。3)白细胞作为缺血脑中自由基的来源。外周环磷酰胺诱导大鼠白细胞减少（1,180/mm^3）。大脑中动脉闭塞3小时后获得的缺血半球切片的化学发光与正常白细胞计数（5,180/mm^3）相比显着减少。

项目成果

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H. Hisamatsu 等人：“脑缺血再灌注过程中血浆 NO 终产物的变化”，12. 127-130 (1994)。

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Kumura E 等人：“大鼠局灶性脑缺血后再灌注过程中亚硝基血红蛋白的产生。”

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Yoshimine, T,et al.：“药物治疗微循环障碍。t-PA。（日语）”Gendai-Iryo。