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,t PA)注射是否可以降低t PA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t PA,或联合注射EPO(800 IU/kg)及t PA。结果局部血管内低剂量EPO联合t PA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t PA注射组与0.9%(质量分数)氯化钠注射液联合t PA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t PA联合使用,可减少t PA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。
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.
出处
《首都医科大学学报》
CAS
2014年第6期748-754,共7页
Journal of Capital Medical University
基金
国家自然科学基金(81071058
81201028
81271461)~~
