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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

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【作者】 刘轲李建生郜利霞宋张杰杨歆科韩向辉刘敬霞刘政国周友龙

【Author】 LIU Ke,LI Jian-Sheng,GAO Li-Xia,et al. The First Affiliated Hospital of Henan College of Traditional Chinese Medicine, Zhengzhou 45000,Henan,China

【机构】 河南中医学院第一附属医院河南中医学院老年医学研究所宁夏医科大学河南省人民医院病理科

【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.

【基金】 国家自然科学基金资助项目(No.30772842;30973744)
  • 【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
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