论文部分内容阅读
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。
Objective To investigate the effect of recombinant human erythropoietin (rhEPO) on angiogenesis after chronic cerebral ischemia in rats. Methods SD rats were randomly divided into sham operation group, ischemia model group, edaravone group (positive control, 10 mg / kg), rhEPO nasal administration group (24 u.40μl-1, And rhEPO nasal administration group (12, 24, 48 u.40 μl-1). Focal cerebral ischemia was induced by middle cerebral artery occlusion in rats. The administration was given 30 min before operation and 2 hrs after operation respectively, once every other day from the second day to 14 days after the operation. 35 days after ischemia, immunohistochemistry was used to detect the number of cells expressing CD31, HIF-1α, VEGF and Flk-1 protein on the ischemic side. Results There was no expression of CD31, HIF-1α, VEGF and Flk-1 protein in sham operation group. The expression of VEGF and Flk-1 protein in ischemic model group was significantly higher than that in sham operation group. Nasal administration of rhEPO (24 and 48 u.40μl-1) The expressions of CD31, HIF-1α and VEGF in the ischemic brain of the drug group were significantly higher than those in the ischemic model group. In addition, nasal administration of rhEPO (24 u.40 μl-1) upregulated the receptor Flk-1 while nasal administration of rhEPO (48 u.40 μl-1) downregulated the receptor Flk-1. Conclusion Nasal administration of rhEPO can enhance the expression of VEGF protein through the HIF-1α pathway and promote the protective effect of angiogenesis on chronic cerebral ischemia in rats.