Zhang Shi-hong, Wei Er-qing, Zhu Chao-yang, Chen Zhong, Zhang Song-fa
Department of Pharmacology, Medical School, Zhejiang University, Hangzhou 310031, China.
Yao Xue Xue Bao. 2004 Jan;39(1):1-4.
To determine the protective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia induced by endothelin-1 in rats.
Slow microinjection of endothelin-1 (120 pmol in 6 microL, 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 i.p. 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.
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.
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.
确定白三烯受体拮抗剂ONO - 1078对内皮素-1诱导的大鼠局灶性脑缺血的保护作用。
通过将内皮素-1(120皮摩尔溶于6微升,注射时间>6分钟)缓慢微量注射到大脑中动脉附近区域来诱导局灶性脑缺血。在注射内皮素-1前1小时腹腔注射ONO - 1078(0.1毫克·千克-1)。缺血24小时后观察神经症状、脑水肿、脑梗死面积以及皮质和纹状体中的存活神经元。
脑内微量注射内皮素-1可诱发明显的神经症状、脑梗死、脑水肿,并导致皮质和纹状体中存活神经元数量减少。在预先用ONO - 1078处理的大鼠中,内皮素-1诱导的脑水肿和脑梗死面积减小。纹状体和皮质中存活神经元的数量显著增加。神经症状有所改善但不明显。
ONO - 1078对内皮素-1诱导的脑缺血损伤具有神经保护作用,因此,白三烯可能在脑缺血损伤中起作用。