【摘要】 目的研究成年大鼠局灶性脑缺血后海马齿状回(DG)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。方法通过大脑中动脉阻断法(MCAO)建立大鼠局灶性脑缺血模型,以5-溴-2-脱氧尿核苷(BrdU)标记增殖的神经前体细胞(NPCs),用免疫组化及免疫荧光双标记法动态检测脑缺血后不同时间DG神经细胞增殖及其分化,同时观察增殖细胞表达VEGF及其受体情况。结果与对照组相比,缺血侧DG的BrdU阳性细胞数在脑缺血后1d开始增加,7d达高峰,28d接近正常水平;BrdU/TuJ1、BrdU/MAP-2阳性双标细胞数在脑缺血后14d开始增加,28d达高峰;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。结论大鼠局灶性脑缺血可激活DG自体NPCs原位增殖、分化,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。更多还原

【Abstract】 Objective To investigate neurogenesis and its relation with VEGF in the dentate gyrus(DG)of the hippocampus after focal cerebral ischemia of adult rats,and to discuss its regulatory mechanism.Methods Focal cerebral ischemia was induced by transient MCAO in adult Wistar rats.BrdU was injected to label dividing cells.Immunohistochemistry and immunofluorescence were used to detect the dynamic expression of BrdU,TuJ1,MAP-2 and GFAP which are the specific markers of endogenous neural precursor cells(NPCs),neurons and astrocytes respectively.Simultaneously,the expression of VEGF and its receptor were observed in newborn NPCs.Results Compared with that of the sham-operated controls,the number of BrdU-positive cells in the DG began to increase at day 1 peakded at day 7,and almost returned to normal at day 28 after ischemia.The number of BrdU/TuJ1 and BrdU/MAP-2 double positive cells began to increase at day 14 after cerebral ischemia,and peaked at day 28.The number of BrdU/GFAP double positive cells remained almost unchanged after cerebral ischemia.In the DG,BrdU labeled cells expressed VEGF and FLK-1.Conclusion Our results indicate that cerebral ischemia promotes the increases of endogenous NPCs and most proliferated cells differentiate into neurons.The expression of endogenously synthesized VEGF and its receptor in newborn NPCs is one of possible mechanisms of proliferation after cerebral ischemia.更多还原