局灶性脑缺血后侧脑室室下区神经发生及其与血管内皮生长因子关系的研究  

Neurogenesis in subventricular zone and correlation between neurogenesis and vascular endothelial cell growth factor after focal cerebral ischemia

作　　者：程海霞[1] 张立平[2] 刘尚明[3] 赵舒武[4] 季冉[2] 吴镇[5] 

机构地区：[1]天津市塘沽中医医院病理科,天津300451 [2]山东大学医学院解剖学教研室,济南250012 [3]山东大学医学院组织胚胎学教研室,济南250012 [4]天津中医药大学组织胚胎学教研室,天津300193 [5]山东大学第二医院检验科,济南250033

出　　处：《神经解剖学杂志》2008年第6期587-591,共5页Chinese Journal of Neuroanatomy

基　　金：山东省自然科学基金(Y99C03)资助项目

摘　　要：为了研究成年大鼠局灶性脑缺血后侧脑室室下区(SVZ)神经发生的情况及其与血管内皮生长因子(VEGF)的关系,探讨脑缺血后神经发生及其调控机制,本研究通过大脑中动脉阻断法(MCAO)建立大鼠局灶性脑缺血模型,5-溴-2-脱氧尿核苷(BrdU)标记增殖的神经前体细胞,用免疫荧光双标记法动态检测BrdU、TuJ1、MAP-2、GFAP的表达,同时观察增殖细胞表达VEGF及其受体情况。结果显示:与对照组相比,大鼠SVZ的BrdU阳性细胞数在脑缺血后4 d组明显增加,14 d组达到高峰;Br-dU/TuJ1、BrdU/MAP-2阳性双标细胞数在脑缺血后14 d组开始增加,28 d组达到高峰;但BrdU/GFAP阳性双标细胞数则无明显变化;增殖的BrdU阳性细胞同时表达VEGF及其受体FLK-1。以上结果提示:大鼠局灶性脑缺血可激活SVZ自体神经前体细胞原位增殖、分化,且增殖的细胞同时表达VEGF及其受体可能是脑缺血后神经发生增强的调节机制之一。To investigate the neurogenesis and the relations about vascular endothelial growth factor （VEGF） and neurogenesis in the SVZ after focal cerebral ischemia of adult rats, to discuss neurogenesis and its regulate mechanism, the focal cerebral ischemia model was induced by transient MCAO in adult rats. BrdU was injected to label dividing endogenous neural precursor cells （NPCs）. Immunofluorescence double-labeled methods were used to detect the dynamic expression of BrdU, TuJ1, microtubule-associated protein-2 （MAP-2） and glial fibrillary acidic protein（GFAP）. Simultaneously, the expression of VEGF and its receptor on newborn NPCs were observed. The present results showed that compared with the sham-operated controls, the number of BrdU-positive cells in the SVZ increased markedly at 4 days, reached peak at 14 days after ischemia; The number of BrdU/TuJ1 and BrdU/MAP-2 double positive cells began to increase 14 days after cerebral ischemia, peaked at 28 days; But the number of BrdU/GFAP double positive cells remained almost unchanged after cerebral ischemia. In the SVZ, there was BrdU labeling in cells expressing VEGF and FLK-1. Our results indicate that cerebral ischemia stimulates the proliferation and differentiation of endogenous NPCs in the SVZ and the expression of VEGF and its receptor on newborn cells is one of possible mechanisms of neurogenesis after cerebral ischemia.

关 键 词：局灶性脑缺血 神经发生 血管内皮生长因子 细胞增殖 大鼠 

分 类 号：R743[医药卫生—神经病学与精神病学]