老龄大鼠脑缺血/再灌注微血管生成及VEGF/VEGFR系统表达变化  

The change of cerebral angiogenesis and VEGF/VEGFR system expression after cerebral ischemia/ reperfusion in the aged rats

作　　者：刘轲[1] 李建生[2] 周友龙[2] 高剑峰[2] 杨歆科[2] 赵跃武[2] 刘政国[2] 刘敬霞[2] 

机构地区：[1]河南中医学院第一附属医院脑病医院,河南郑州450000 [2]河南中医学院老年医学研究所

出　　处：《中国老年学杂志》2010年第20期2931-2935,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金资助项目(30171812);河南省杰出青年基金资助项目(0612000700)

摘　　要：目的从血管内皮生长因子（VEGF）/VEGFR系统因子表达方面揭示老年脑缺血/再灌注（I/R）损伤及脑微血管生成机制。方法 SD青年和老龄大鼠,随机分为青年假手术组、青年模型组、老龄假手术组、老龄模型组,模型组分为缺血（I）3 h、I/R 1 d、3 d、6 d、12 d时间点。采用线栓法制备局灶性脑I/R模型,运用免疫组化和原位杂交等技术测定脑微血管密度（MVD）、微血管场面积,VEGF、Flt-1、Flk-1的蛋白及其mRNA表达。结果老龄模型组MVD自I 3 h逐渐下降至I/R 12 d;血管场面积I/R 1 d达峰值,后逐步下降。VEGF表达I/R 1 d达峰值,逐步减弱至I/R3 d,I/R 6 d稍有增强,后明显减弱;Flt-1、Flk-1表达I/R 1 d达峰值后迅速。VEGF、Flt-1、Flk-1 mRNA表达随再灌注时间延长逐步增强,均于I/R 1 d达峰值;VEGF mRNA表达I/R1~3 d逐步减弱,后缓慢增强;Flt-1、Flk-1 mRNA表达I/R1 d后迅速减弱。结论老年I/R损伤后脑微血管生成能力明显减弱,其机制可能与VEGF、Flt-1、Flk-1的蛋白及其基因表达减弱有关,增龄可能是导致VEGF/VEGFR系统因子表达减弱的主要原因之一。Objective To reveal the mechanism of angiogenesis after cerebral ischemia/ reperfusion（I/R） in aged from the expression of system factor of VEGF/VEGFR.Methods The youth male SD rats（5~6 months） and the aged male SD rats（20~21 months） were divided randomly into youth sham-operation,youth model,old age sham-operation,old age model groups,model groups were divided into I 3 h,I/R 1,3,6,12 d time spots.The line hitch law preparation focal cerebral I/R model were used to examine microvessel density（MVD）,microvessel area,and the expression of protein and mRNA of VEGF,Flt-1,Flk-1 by immunohistochemistry and in situ hybridization.Results The MVD of old age model group began to decline at I 3 h,continued to I/R 12 d, the microvessel area reached the peak at I/R 1 d,and then decreased gradually. The expression of VEGF was achieved the peak at I/R 1 d,weakened at I/R 3 d,strengthened at I/R 6 h,and decreased rapidly.The expression of Flt-1 was reached the peak at I/R 1 d,and then declined rapidly.The expressions of VEGF mRNA was gradually weakened from I/R 1~3 d,and then strengthened,the Flt-1 mRNA expression was rapidly declined after I/R 1d.Conclusions The old age brain I/R into the damage cerebellum capillaries generative capacity is weaken obviously again,its mechanism may be related to vascular growth factor VEGF,Flt-1,Flk-1 which protein and gene expression reduced,increasing the age is one of the major factors which may lead to the expression of VEGF/VEGFR system factor expression weaken.

关 键 词：老龄 大鼠 脑缺血/再灌注 血管生成 血管内皮生长因子 Fms样酪氨酸激酶-1 胚胎肝激酶-1 

分 类 号：R743.32[医药卫生—神经病学与精神病学]