局部血管内低剂量促红细胞生成素和联合tPA注射对大鼠脑缺血的影响

doi:10.3969/j.issn.1006-7795.2014.06.014

摘要/Abstract

摘要：

目的探讨局部血管内低剂量促红细胞生成素(erythropoietin,EPO)联合组织纤溶酶原激活剂(tissue plasminogen activator,tPA) 注射是否可以降低tPA单独应用时的不良反应及机制。方法成年雄性Sprague-Dawley大鼠进行大脑中动脉闭塞手术,将健康雄性SD大鼠按数字表法随机分为5组,每组10只,分别缺血2 h和4 h,再灌注30 min后通过大脑中动脉单独注射tPA,或联合注射EPO(800 IU/kg)及tPA。结果局部血管内低剂量EPO联合tPA注射可以减小大鼠脑缺血再灌注24 h后的病死率、改善神经功能、减少脑水肿和脑出血,并且没有产生血液学不良反应。局部血管内低剂量EPO联合tPA注射组与0.9%(质量分数)氯化钠注射液联合tPA注射组比较,p-AKT和p-ERK的表达水平明显升高。结论大鼠脑缺血后,局部血管内低剂量EPO和tPA联合使用,可减少tPA单独使用时的不良反应,并发挥EPO的神经保护作用,可能与AKT和ERK通路激活有关。

关键词: 促红细胞生成素, 组织纤溶酶原激活剂, 神经保护, 脑缺血, 再灌注

Abstract:

Objective To investigate the effect of local intraarterial infusion of low-dose erythropoietin(EPO) in combination with tissue plasminogen activator(tPA) on focal cerebral ischemic stroke. Methods Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 or 4 h, followed by a tPA infusion over 30 min at the onset of reperfusion, with or without EPO(800 IU/kg) infusion via middle cerebral artery. A total of 50 male rats were randomly divided into 5 groups. Results Local intraarterial infusion of low-dose EPO in combination with tPA protected against transient focal cerebral ischemia in rats, manifested by a decrease in mortality, neurological deficit scores, brain edema and hemorrhage with no hematological side effects after 24 h reperfusion. The levels of p-AKT and p-ERK were both increased in response to administration of EPO, suggesting a concurrent activation of AKT and ERK pathways. Conclusion Local intraarterial infusion of low-dose EPO in combination with tPA protected against focal cerebral ischemia in rats with no significant side effects, involving activation of AKT and ERK pathways.

Key words: erythropoietin, tissue plasminogen activator, neuroprotection, cerebral ischemia, reperfusion

中图分类号:

R743.31

王荣亮, 赵海苹, 武晓宁, 高金环, 吉训明, 罗玉敏. 局部血管内低剂量促红细胞生成素和联合tPA注射对大鼠脑缺血的影响[J]. 首都医科大学学报, 2014, 35(6): 748-754.

Wang Rongliang, Zhao Haiping, Wu Xiaoning, Gao Jinhuan, Ji Xunming, Luo Yumin. Effect of local intraarterial infusion of low-dose erythropoietin in combination with tissue plasminogen activator on focal cerebral ischemia in rats[J]. Journal of Capital Medical University, 2014, 35(6): 748-754.

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