【摘要】 目的探讨重组人促红细胞生成素(rhEPO)对大鼠慢性脑缺血后血管生成的作用。方法 SD大鼠随机分为假手术组、缺血模型组、依达拉奉组(阳性对照,10 mg/kg)、灭活rhEPO鼻腔给药组(24 u.40μl-1,加热灭活)和rhEPO鼻腔给药组(12、24、48 u.40μl-1)。以大脑中动脉栓塞诱导大鼠局灶性脑缺血,手术当日术前30 min和术后2 h各给药1次,第2天起隔天1次至术后14天。缺血后35天,应用免疫组织化学方法检测缺血侧CD31、HIF-1α、VEGF和Flk-1蛋白表达的细胞数目。结果假手术组无CD31、HIF-1α、VEGF和Flk-1蛋白表达,缺血模型组较假手术组表达明显增加,依达拉奉组和rhEPO(24和48 u.40μl-1)鼻腔给药组缺血侧大脑CD31、HIF-1α和VEGF蛋白的表达与缺血模型组比较明显增高。另外,rhEPO(24 u.40μl-1)鼻腔给药使受体Flk-1上调,而rhEPO(48 u.40μl-1)鼻腔给药使受体Flk-1下调。结论 rhEPO鼻腔给药可通过HIF-1α途径增强VEGF蛋白的表达、促进血管生成发挥对大鼠慢性脑缺血的保护作用。更多还原

【Abstract】 Objective To investigate the effect of erythropoietin on angiogenesis after chronic cerebral ischemia in rats.Methods The Sprague Dawley rats were divided into 5 groups randomly: sham group,model group,edaravone group,intranasal administration inactivation rhEPO 24 u ·40 μl-1 group and rhEPO 12,24,48 u ·40 μl-1 group.Focal cerebral ischemia in rats was induced by middle cerebral artery occlusion(MCAO).Drugs were administrated 30 minutes before and 2 hours after operation.From the second day,they were administrated qod.for 2 weeks.The expressed cell number of positive protein of CD31,HIF-1α,VEGF and Flk-1 was detected by immunohistochemistry methods in the ischemic region at 35 days after ischemia.Results There was no protein of CD31,HIF-1α,VEGF and Flk-1 expressed in sham group in the ischemic region.The expression number of these proteins was increased in model group.But edaravone group and rhEPO groups administrated intranasal(24 u·40 μl-1 and 48 u·40 μl-1) further increased the expressed protein number of CD31,HIF-1α and VEGF.Compared with model group,there were significant differences.The Flk-1 receptor was up-regulated by rhEPO group intranasal administration(24 u·40 μl-1),but down-regulated by rhEPO group intranasal administration(48 u·40 μl-1).Conclusion The rhEPO intranasal administration can promote angiogenesis to exert protective effect on cerebral ischemia,which could be relative with HIF-1α pathway to enhance the expression of VEGF.更多还原