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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
【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。
【Abstract】 Objective To observe the mechanism of angio genesis after cerebral ischemia/ reperfusion(I/R) in aged from the expression o f system factor of Ang/Tie-2. Methods The youth male SD rats(5~ 6 months) and the age d 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 preparati on focal cerebral I/R model were used to examine microvessel density(MVD),micr ovessel area and the expressions of protein and mRNA of Ang-1,Ang-2,Tie-2 b y immunohistochemistry and in situ hybridization. Results The MVD of old age model group began to dec line 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 p eak a t I/R 3d,and then decreased gradually.The expression of Ang-2 was achi ev ed the peak at I/R 1 d,weakened at I/R 3 d,and then decreased gradually.The e xpression of Ang-1 mRNA was achieved the peak at I/R 3 d,and then decreased gr a dually.The expressions of Ang-2 mRNA was gradually weakened from I/R 1~3 d,a nd 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 mec hanism may be related to vascular growth factor Ang-1,Ang-2,Tie-2 which prot ein 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.
【Key words】 Cerebral ischemia/reperfusion; Angiogenesis; Angipoietin-1; Angip oietin-2; Tyrosine kinase receptor-2;
- 【文献出处】 中国老年学杂志 ,Chinese Journal of Gerontology , 编辑部邮箱 ,2013年03期
- 【分类号】R363
- 【被引频次】10
- 【下载频次】253