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

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。

Effect of local intraarterial infusion of low-dose erythropoietin in combination with tissue plasminogen activator on focal cerebral ischemia in rats

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.