半胱氨酰白三烯受体拮抗剂pranlukast对小鼠局灶性脑缺血的治疗作用  

Therapeutic effect of pranlukast,a cysteinyl leukotriene receptor antagoist,on focal cerebral ischemia in mice

作　　者：徐秋琴[1] 魏尔清[2] 俞月萍[3] 张琦[3] 张世红[2] 朱朝阳[2] XU Qiu-qin;WEI Er-qing;YU Yue-ping;ZHANG qi;ZHANG Shi-hong;ZHU Chao-yang(Dept of Pharmacology,School of Medicine,Zhejiang University,Hangzhou 310031,China;Dept of Pharmacology,Medical School,Hangzhou Teachers College,Hangzhou 310012,China;Dept of Pharnuwology,Zhejiang Medical College,Hangzhou 310053,China)

机构地区：[1]杭州师范学院医学院药理学教研室,浙江杭州310012 [2]浙江大学医学院药理学教研室,浙江杭州310031 [3]浙江医学高等专科学校药理学教研室,浙江杭州310053

出　　处：《中国药理学通报》2004年第7期758-761,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目;No 30271498;浙江省自然科学基金资助项目;No 39909

摘　　要：目的观察半胱氨酰白三烯受体拮抗剂pranlukast(ONO 1078)在小鼠局灶性脑缺血后的治疗作用。方法采用大脑中动脉阻塞造成小鼠持续性局灶性脑缺血,缺血后1、6、24h分别给小鼠腹腔注射pranlukast或依达拉奉,观察药物对缺血24、48h后的神经功能缺损症状,48h后的脑梗死体积、两侧大脑半球比值、神经元密度的影响。结果Pranlukast 01、02mg·kg-1及依达拉奉3、10mg·kg-1均能减轻神经症状、减小脑梗死体积、降低缺血侧/非缺血侧大脑半球比值、减轻海马CA1区、皮层和纹状体的神经元密度降低。结论Pranlukast脑缺血后给药对脑损伤有治疗作用,提示有治疗缺血性脑卒中的临床前景。Aim To determine whether pranlukast(ONO-1078),a cysteinyl leukotriene receptor antagonist,possesses therapeutic effect when administered after focal cerebral ischemia in mice.Methods Persistent focal cerebral ischemia was induced by middle cerebral artery occlusion.Pranlukast and edaravone,a positive control drug,were ip injected 1,6 and 24 h after ischemia.The neurological deficits were evaluated by neurological scores and inclined plane test 24 and 48 h after the surgery.Forty-eight h later,the brain slices were prepared for measurements of infarct volume and the ratio of ischemic/non-ischemic hemispheres.Brain sections were cut and examined for neuron densities in different regions of the brain.The effects of pranlukast and edaravone were evaluated by the changes of these variables.Results Pranlukast(0.1 and 0.2 mg·kg-1)and edaravone(3 and 10 mg·kg-1)significantly reduced the neurological deficits,infarct volume(maximally 82.3%),ratio of ischemic/non-ischemic hemispheres,and attenuated the reduction of neuron densities in hippocampal CA1 region,cortex and striatum.Conclusion Pranlukast possesses therapeutic effect on ischemic insults when administered after ischemia as effective as edravone,indicating a therapeutic potential in the treatment of ischemic stroke.

关 键 词：脑缺血 脑水肿 半胱氨酰白三烯受体拮抗剂 pranlukast{ONO-1078 4-氧-8-[对-(4-苯丁氧基)苯甲酰氨基]-2-(5-四唑基)-4H-1-苯并吡喃半水化合物} 依达拉奉(MCI186 3-甲基-1-苯基-2-吡唑啉-5-酮基) 

分 类 号：R-332[医药卫生] R322.81