老龄大鼠脑缺血/再灌注微血管生成及Ang/Tie-2系统的表达变化  

Change of cerebral angiogenesis and Ang/Tie-2 system expression after cerebral ischemia/reperfusion in the aged rats

作　　者：刘轲[1] 李建生[2] 郜利霞[1] 宋张杰[1] 杨歆科[1] 韩向辉[1] 刘敬霞[3] 刘政国[4] 周友龙[2] 

机构地区：[1]河南中医学院第一附属医院,河南郑州450000 [2]河南中医学院老年医学研究所 [3]宁夏医科大学 [4]河南省人民医院病理科

出　　处：《中国老年学杂志》2013年第3期584-588,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金资助项目(No.30772842;30973744)

摘　　要：目的从血管生成素(Ang)/酪氨酸激酶型受体(Tie)-2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、3、6、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,Ang-1、Ang-2、Tie-2的蛋白及其mR-NA表达。结果老龄模型组MVD自I 3 h逐渐降低至I/R 12 d;血管场面积I/R 1 d至高峰,后逐步降低。Ang-1表达于I/R 3 d至高峰,随后逐步降低;Ang-2表达I/R 1 d至高峰,逐步降低至I/R 3 d,I/R 6 d稍有增高,后明显降低;Tie-2表达I/R 1 d至高峰,随后逐步降低。Ang-1 mRNA表达于I/R 3 d至高峰,随后逐步降低;Ang-2 mRNA表达I/R 1～3 d逐步降低,后缓慢增高;Tie-2 mRNA表达于I/R 3 d至高峰,随后明显降低。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Ang-1、Ang-2、Tie-2的蛋白及其基因表达减弱有关,增龄可能是导致Ang/Tie-2系统因子表达减弱的主要原因之一。Objective To observe the mechanism of angiogenesis after cerebral ischemia/ reperfusion （I/R） in aged from the expression of system factor of Ang/Tie-2. 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 expressions of protein and mRNA of Ang-1, Ang-2 ,Tie-2 by immunohistochemistry and in situ hybridiza- tion. 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 Ang-1 was achieved the peak a t I/R 3d, and then decreased gradually. The expression of Aug-2 was achieved the peak at I/R 1 d, weakened at I/R 3 d, and then decreased gradually. The expression of Ang-1 mRNA was achieved the peak at I/R 3 d, and then decreased gradually. The expressions of Ang-2 mRNA was gradually weakened from I/R 1 ~ 3 d, and then strengthened. The expression of Tie-2 mRNA was achieved the peak a t I/R 3 d and then decreased gradually. Conclusions The damage cerebellum capillaries generative capacity resulted from old age brain I/R is weaken obviously, its mechanism may be related to vascular growth factor Ang-1, Ang-2 ,Tie-2 which protein and gene expression are reduced, increasing the age is one of the major factors which may lead to the expression of Ang/Tie-2 system factor expression weaken.

关 键 词：脑缺血 再灌注 血管生成 血管生成素-1 血管生成素-2 酪氨酸激酶型受体-2 

分 类 号：R749[医药卫生—神经病学与精神病学]