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白三烯受体拮抗剂ONO - 1078对大鼠内皮素-1诱导的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].

作者信息

Zhang Shi-hong, Wei Er-qing, Zhu Chao-yang, Chen Zhong, Zhang Song-fa

机构信息

Department of Pharmacology, Medical School, Zhejiang University, Hangzhou 310031, China.

出版信息

Yao Xue Xue Bao. 2004 Jan;39(1):1-4.

Abstract

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 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.

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.

摘要

目的

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。

方法

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。

结果

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。

结论

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。

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