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白三烯拮抗剂ONO-1078对小鼠持续性局灶性脑缺血的作用

Effect of ONO-1078, a leukotriene antagonist, on permanent focal cerebral ischemia in mice

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【作者】 王仁定张纬萍王苹丽曾玲晖魏尔清

【Author】 Wang Rending (Wang RD), Zhang Weiping (Zhang WP),Wang Pingli (Wang PL), et al (Laboratory of Neurobiology, Medical School, Zhejiang University, Hangzhou 310031)

【机构】 浙江大学医学院神经生物学实验室浙江大学医学院神经生物学实验室 杭州310031杭州310031

【摘要】 目的 :在小鼠模型研究白三烯拮抗剂 { 4 -氧 - 8- [对 - (4-苯丁氧基 )苯甲酰氨基 ]- 2 - (5 -四唑基 ) - 4 H- 1-苯并吡喃半水合物(ONO- 10 78) }对脑缺血的保护作用。方法 :以大脑中动脉阻塞法诱导持续性局灶性脑缺血。在脑缺血前 30 min和缺血后 6 0 min腹腔注射 ONO- 10 78、尼莫地平或生理盐水 (对照 )。脑缺血 2 4 h后 ,观察神经症状 ,并测定脑湿重和脑梗死体积。结果 :ONO-10 78(0 .0 1,0 .0 3,0 .1mg· kg- 1 )和尼莫地平 (0 .2 mg· kg- 1 )减少脑梗死体积 ;ONO- 10 78(0 .1mg kg- 1 )减轻脑湿重 ,尼莫地平无此作用 ;ONO- 10 78和尼莫地平对神经症状无明显作用。结论 :ONO- 10 78对持续性局灶性脑缺血有保护作用 ,提示白三烯拮抗剂可作为急性脑缺血的一种新治疗药

【Abstract】 OBJECTIVE:To determine whether ONO 1078{ 4 oxo 8 [p (4 phenylbntyloxy)benzoyl amino] 2 (tetrazd 5 yl) 4H 1 benzopyran hemihydrate},a potent leukotriene antagonist, has a protective effect on focal cerebral ischemia in a mouse model. METHOD:Focal cerebral ischemia was induced by permanent middle cerebral artery (MCA) occlusion in male ICR mice. ONO 1078, nimodipine or saline (control) was injected intraperitoneally 30 min before and 60 min after MCA occlusion. Twenty four hours later, the neurological symptoms were observed, brains were weighted, and infarct volumes were measured by computer imaging analysis. RESULTS:ONO 1078 (0.01, 0.03, 0.1 mg kg -1 ) reduced the infarct volume dose dependently, and nimodipine also had the effect. ONO 1078 (0.1mg kg -1 ), not nimodipine, also reduced the increase ment of brain wet weights. No significant changes were observed in neurological scores. CONCLUSION:ONO 1078 has the protective effect on focal cerebral ischemia, this may suggest a novel approach to the treatment of acute cerebral ischemia.

【基金】 国家自然科学基金项目 (No.3 9770 2 70 )资助
  • 【文献出处】 中国现代应用药学 ,Chinese Journal of Modern Applied Pharmacy , 编辑部邮箱 ,2001年06期
  • 【分类号】R965
  • 【被引频次】9
  • 【下载频次】50
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