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表皮生长因子促进脑梗死后室管膜下区神经干细胞迁徙机制的初步研究

Intraventricular infusion of exogenous epidermal growth factor improves proliferation and migration of endogenous neural stem cells in adult rat brains with neocortex infarction

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【作者】 余剑曾进胜赵湛熊丽何扬东黄如训

【Author】 YU Jian ZENG Jin-sheng ZHAO Zhan (Stroke Center,Department of Neurology,First University Hospital,Sun Yet-Sen University,Guangzhou 510080,China)

【机构】 中山大学附属第一医院神经科脑血管专科中山大学附属第一医院神经科脑血管专科 广东广州510080广东广州510080

【摘要】 目的观察表皮生长因子(EGF)对大鼠脑梗死后室管膜下区(SVZ)神经干细胞(NSCs)的调节作用。方法采用肾血管性高血压大鼠复制成一侧大脑中动脉皮层支闭塞(MCAO)模型。MCAO术后24h,64只EGF组大鼠侧脑室注入10μ1 EGF(0.1μg/μ1),连续2d,共2μg;64只vehicle组大鼠只注入不含EGF的等量溶液。MCAO术后1、2、3和4周,免疫组化检测SVZ内巢蛋白(nestin),Western blotting检测双侧半球nestin、神经细胞粘附分子(NCAM)和瑞林蛋白(reelin)表达。结果与同期vehicle组相比,EGF组大鼠梗死灶同侧SVZ内nestin染色更强,可见从SVZ沿胼胝体向梗死灶迁徙的nestin阳性细胞带;Western blotting显示EGF促使脑梗死灶同侧nestin、NCAM和reelin更早期和更高的表达(P<0.05)。结论EGF可能通过促使卒中后nestin、NCAM和rcelin等神经可塑性物质的早期高峰表达而调节SVZ内NSCs增殖和向梗死灶迁徙。

【Abstract】 Objective To observe the modulation to proliferation and migration of neural stem cells(NSCs) in Subventricular Zone(SVZ)after cerebral infarction and after intraventricular infusion of exogenous EGF,and ex- plore the internal mechanism of neural plasticity.Methods One day after the right middle cerebral artery occlu- sion(MCAO)in renovascular hypertensive rats,tenul EGF(0.1μg/μl)was infused consecutively into lateral ven- tricle in 64 experimental rats(EGF group) and the same amount of vehicle in 64 MCAO rats as controls for 2 days.At the end of 1,2,3,and 4 weeks after the MCAO,the brains of eight rats from each group respectively were taken,and sectioned for nestin detection by immunohistochemistry,or homogenated for the detection of nestin,neu- ral cell adhension molecule(NCAM)and reelin by western blotting.Sham controls were matched at the baseline. Results Intraventricular infusion of EGF resulted in distinct increase of the density of nestin staining in the cells of the SVZ ipsilateral to infarct cavity relative to vehicle control.Nestin positive cells migrated away from the walls of the lateral ventricle towards infarct cavity in sequence along corpus callosum.EGF hastened earlier and higher peak expression of nestin,NCAM and reelin in the brain ipsilateral to infarct cavity than in vehicle control by western blotting(P<0.05).Conclusion EGF promotes NSCs in the SVZ to proliferate and to migrate to in- farct cavity.EGF maybe adjusts neural plasticity by promoting early and high peak expression of nestin,NCAM and reelin in the brain ipsilateral to infarct cavity.

【基金】 美国CMB基金(00-730);国家自然科学基金(39940012,30271485);卫生部临床学科重点项目(2004);广东省医药卫生科研基金(B2003031);教育部高校青年教师奖资助项目(TRAPOYT,2002年);教育部归国人员启动基金(1999363);广东省自然科学基金攻关项目资助项目(2003B30301,B30303)
  • 【文献出处】 中风与神经疾病杂志 ,Journal of Apoplexy and Nervous Diseases , 编辑部邮箱 ,2007年01期
  • 【分类号】R743.3
  • 【被引频次】8
  • 【下载频次】241
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