1研发背景上世纪30年代发现动物致敏后体内产生不稳定的化学物质,称作慢反应物质,1960年Brockelhurst揭示这是免疫系统在受到抗原攻击产生的内源性物质,可引起平滑肌(如气道和十二指肠)收缩,称之为过敏性慢反应物质(SRS-A)(Brocklehurst...1研发背景上世纪30年代发现动物致敏后体内产生不稳定的化学物质,称作慢反应物质,1960年Brockelhurst揭示这是免疫系统在受到抗原攻击产生的内源性物质,可引起平滑肌(如气道和十二指肠)收缩,称之为过敏性慢反应物质(SRS-A)(Brocklehurst WE.The release of histamine and formation of a slow reacting substance(SRS-A)during anaphylactic shock.J Physiol,1960,151:416-435)。20世纪70年代证实SRS-A是由花生四烯酸(AA)代谢生成的3个肽白三烯(peptidyl leucotrienes)(简称白三烯),即LTC4、LTD4和LTE4,三者之差异是在二十碳四烯酸中分别连接3、2、1个氨基酸(图1)。白三烯的生理作用是引起呼吸道平滑肌收缩和增加肺泡的通透性以及黏膜上皮细胞分泌等,导致哮喘和过敏性疾病。展开更多
AIM To determine whether ONO 1078 {pranlukast, 4 oxo 8 [p (4 phenylbutyloxy) benzoyl amino] 2 (tetrazol 5 yl) 4H 1 benzopyran hemihydrate}, a potent leukotriene antagonist, has protective effect on focal cerebral isch...AIM To determine whether ONO 1078 {pranlukast, 4 oxo 8 [p (4 phenylbutyloxy) benzoyl amino] 2 (tetrazol 5 yl) 4H 1 benzopyran hemihydrate}, a potent leukotriene antagonist, has protective effect on focal cerebral ischemia in mice. METHODS Focal cerebral ischemia was induced by permanent middle cerebral artery (MCA) occlusion in mice. ONO 1078 (0 01, 0 05, 0 10 mg·kg -1 ), dexamethasone (0 5 mg·kg -1 ), nimodipine (0 2 mg·kg -1 ) or saline (control) were injected ip once daily for 3 days, and 30 min before MCA occlusion. Twenty four hours after cerebral ischemia, the neurological scores were evaluated, infarct volumes and areas of the right and left cerebral hemispheres were measured by computer imaging analysis. RESULTS ONO 1078, dexamethasone and nimodipine reduced the neurological scores. ONO 1078 and dexamethasone reduced the ratio of right/left hemisphere area, indicating inhibition of brain edema, while nimodipine showed no effect. ONO 1078 dose dependently reduced infarct size, and dexamethasone and nimodipine showed the same effect. CONCLUSION ONO 1078 showed protective effect on focal cerebral ischemia. This may represent a novel approach to the treatment of acute cerebral ischemia.展开更多
文摘1研发背景上世纪30年代发现动物致敏后体内产生不稳定的化学物质,称作慢反应物质,1960年Brockelhurst揭示这是免疫系统在受到抗原攻击产生的内源性物质,可引起平滑肌(如气道和十二指肠)收缩,称之为过敏性慢反应物质(SRS-A)(Brocklehurst WE.The release of histamine and formation of a slow reacting substance(SRS-A)during anaphylactic shock.J Physiol,1960,151:416-435)。20世纪70年代证实SRS-A是由花生四烯酸(AA)代谢生成的3个肽白三烯(peptidyl leucotrienes)(简称白三烯),即LTC4、LTD4和LTE4,三者之差异是在二十碳四烯酸中分别连接3、2、1个氨基酸(图1)。白三烯的生理作用是引起呼吸道平滑肌收缩和增加肺泡的通透性以及黏膜上皮细胞分泌等,导致哮喘和过敏性疾病。
文摘AIM To determine whether ONO 1078 {pranlukast, 4 oxo 8 [p (4 phenylbutyloxy) benzoyl amino] 2 (tetrazol 5 yl) 4H 1 benzopyran hemihydrate}, a potent leukotriene antagonist, has protective effect on focal cerebral ischemia in mice. METHODS Focal cerebral ischemia was induced by permanent middle cerebral artery (MCA) occlusion in mice. ONO 1078 (0 01, 0 05, 0 10 mg·kg -1 ), dexamethasone (0 5 mg·kg -1 ), nimodipine (0 2 mg·kg -1 ) or saline (control) were injected ip once daily for 3 days, and 30 min before MCA occlusion. Twenty four hours after cerebral ischemia, the neurological scores were evaluated, infarct volumes and areas of the right and left cerebral hemispheres were measured by computer imaging analysis. RESULTS ONO 1078, dexamethasone and nimodipine reduced the neurological scores. ONO 1078 and dexamethasone reduced the ratio of right/left hemisphere area, indicating inhibition of brain edema, while nimodipine showed no effect. ONO 1078 dose dependently reduced infarct size, and dexamethasone and nimodipine showed the same effect. CONCLUSION ONO 1078 showed protective effect on focal cerebral ischemia. This may represent a novel approach to the treatment of acute cerebral ischemia.
