白三烯受体拮抗剂ONO-1078对大鼠短暂性全脑缺血的神经保护作用  

作　　者：张丽慧 魏尔清 

机构地区：[1]MedicalSchool,HangzhouTeachersCollege,Hangzhou310012,China [3]DepartmentofPharmacology,SchoolofMedicine,ZhejiangUniversity,Hangzhou310031

出　　处：《Acta Pharmacologica Sinica》2003年第12期1241-1247,共7页中国药理学报（英文版）

摘　　要：AIM: To determine whether ONO-1078 {pranlukast, 4-oxo-8-[p-(4-phenylbutyloxy)benzoyl-amono]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate), a potent leukotriene receptor antagonist, possesses a neuroprotective effect on global cerebral ischemia in rats, and to explore its possible mechanism of action. METHODS: Transient global cerebral ischemia was induced by four-vessel occlusion for 10 min and followed by 72-h reperfusion. ONO-1078(0.03-0.3mg/kg) and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one, a neuroprotective agent) 10 mg/kg were ip injected 30 rain before ischemia and 1 h after reperfusion, and once a day afterward. Neurological outcome was evaluated before ischemia and 24, 48, 72 h after reperfusion. Neuron density, the expressions of N-methyl-D-aspartate (NMDA) receptor subunit proteins (NR1, NR2A, NA2B) and vascular cell adhesion molecule 1 (VCAM-1) in the cerebral cortex and hippocampus were measured at 72h after reperfusion. RESULTS: ONO-1078 (0.1,0.3mg/kg) and edaravone (10 mg/kg) improved ischemia-induced neurological deficiency and reduced neuron death.ONO-1078 (0.1, 0.3mg/kg) significantly inhibited the enhanced expression of NMDA receptor subunit protein NR2A in the cortex and VCAM-1 in the hippocampus of ischemic rats. CONCLUSION: ONO-1078 possesses a neuroprotective effect on global cerebral ischemia in rats, and its mechanism may be partly related to the inhibition of the upregulation of NR2A and VCAM- 1 in different regions of the brain.

关 键 词：白三烯受体拮抗剂 ONO-1078 大鼠 短暂性全脑缺血 神经保护 神经细胞 

分 类 号：R965[医药卫生—药理学]