白三烯受体拮抗剂ONO-1078对内皮素-1诱导的大鼠局灶性脑缺血的保护作用  

Protective effect of ONO-1078,a leukotriene receptor antagonist,on focal cerebral ischemia induced by endothelin-1 in rats

作　　者：张世红[1] 魏尔清[1] 朱朝阳[1] 陈忠[1] 张松法[1] 

机构地区：[1]浙江大学医学院药理学教研室,浙江杭州310031

出　　处：《药学学报》2004年第1期1-4,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 (3 9770 2 70 );江省自然科学基金资助项目 (3 990 90 )

摘　　要：目的　观察白三烯受体拮抗剂ONO 10 78对内皮素 1诱导的大鼠局灶性脑缺血的保护作用。方法　向大脑中动脉附近微量缓慢注射内皮素 1( 12 0pmol,6 μL ,>6min) ,诱导大鼠局灶性脑缺血模型 ,在注射内皮素 1前 1hipONO 10 78( 0 1mg·kg- 1 )。观察神经症状、脑水肿程度、脑梗死体积、纹状体和皮层的存活神经元数的变化。结果脑内微量注射内皮素 1引起动物出现明显神经症状、脑梗死、脑水肿及皮层和纹状体的存活神经元减少。预先ipONO 10 78显著抑制脑水肿 ,减小脑梗死体积 ,增加纹状体和皮层的存活神经元数 ,可减轻神经症状 ,但无显著意义。结论　ONO 10 78对内皮素 1诱导的脑缺血损伤有保护作用 ,白三烯参与了脑缺血后的组织损伤过程。Aim To determine the protective effect of ONO 1078, a leukotriene receptor antagonist, on focal cerebral ischemia induced by endothelin 1 in rats. Methods Slow microinjection of endothelin 1 (120 pmol in 6 μL, for >6 min) into the region near the middle cerebral artery was used to induce focal cerebral ischemia. ONO 1078 (0 1 mg·kg -1 ) was ip injected 1 h before endothelin 1 injection. Neurological symptoms, brain edema, brain infarction size, and the survival neurons in cortex and striatum were observed 24 h after ischemia. Results Intracerebral microinjection of endothelin 1 induced remarkable neurological symptoms, brain infarction, brain edema, and decrease of survival neurons in the cortex and striatum. In rats pretreated with ONO 1078, endothelin 1 induced brain edema and brain infarction size were decreased. The numbers of survival neurons in striatum and cortex were increased significantly. The neurological symptoms were improved but not significantly. Conclusion ONO 1078 possesses neuroprotective effect against cerebral ischemic injury induced by endothelin 1, therefore, leukotrienes may play a role in the injury of cerebral ischemia.

关 键 词：白三烯受体拮抗剂 ONO-1078 内皮素-1 大鼠 局灶性脑缺血 保护作用 

分 类 号：R743.31[医药卫生—神经病学与精神病学]