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).

本研究在脑缺血微循环障碍的病理生理学和治疗方面提供了以下三方面的重要信息：1)局灶性脑缺血时一氧化氮(NO)的产生。结果表明，脑缺血2小时和缺血2小时后再灌流30分钟，脑组织中NO_3~-含量显著升高。N-硝基-L-精氨酸(L-NAME，20 mg/kg)可阻断NO_3~-的这种增加。2)SOD改善微循环。给予重组人铜锌超氧化物歧化酶使大鼠大脑中动脉闭塞后3小时血浆灌流的微血管长度增加。3)白细胞作为缺血脑内自由基的来源。环磷酰胺诱导大鼠外周血白细胞减少(1180/mm^3)。大鼠大脑中动脉闭塞3h后，缺血侧脑片的化学发光强度明显低于正常白细胞计数(5180个/mm~3)。

项目成果

久松英嗣,他: "脳虚血再潅流におけるplasma NO end productsの変動." Cyto-protection and biology. 12. 127-130 (1994)

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)。

Kumura E,et al.: "Nitrosyl hemoglobin production during reperfusion after focal cerebral ischemia in rats." Neurosci Lett. 177. 165-167 (1994)

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。”

早川 徹: "低酸素性神経細胞傷害に対する神経栄養因子の保護作用-in vitro modelを中心に-" Brain Hypoxia. 8. 85-94 (1994)

Toru Hayakawa：“神经营养因子对缺氧神经元损伤的保护作用 - 关注体外模型”Brain Hypoxia。 8. 85-94 (1994)

Isaka T: "Altered expression of antithrombotic molecules in human glioma vessels." Acta Neuropathol(Berl). 87. 81-85 (1994)

Isaka T：“人类神经胶质瘤血管中抗血栓分子的表达发生改变。”

Yoshimine, T,et al.: "Treatment of microcirculatory disturbances by drugs. t-PA.(in Japanese)" Gendai-Iryo. 26. 1124-1129 (1994)

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