白三烯拮抗剂ONO-1078对小鼠持续性局灶性脑缺血的作用

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)-4H-1-苯并吡喃半水合物(ONO-1078)}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30min和缺血后60min腹腔注射ONO-1078、尼莫地平或生理盐水(对照).脑缺血24h后,观察神经症状,并测定脑湿重和脑梗死体积.结果ONO-1078(0.01,0.03,0.1mgkg-1)和尼莫地平(0.2 mg*kg-1)减少脑梗死体积;ONO-1078(0.1 mg kg-1)减轻脑湿重,尼莫地平无此作用;ONO-1078和尼莫地平对神经症状无明显作用.结论ONO-1078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.

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

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.