葛夕洪,杨晶,徐锐,王永利,司同国,贺能树.MMP-2、MMP-9、TIMP-1在血管成形术后再狭窄中的表达及其意义的实验研究[J].中国介入影像与治疗学,2008,5(3):165-169
MMP-2、MMP-9、TIMP-1在血管成形术后再狭窄中的表达及其意义的实验研究
Expression and significance of MMP-2, MMP-9 and TIMP-1 during restenosis after angioplasty: an experimental study
投稿时间:2008-02-02  修订日期:2008-03-19
DOI:
中文关键词:  再狭窄  重塑  基质金属蛋白酶-2  基质金属蛋白酶-9  基质金属蛋白酶抑制剂-1
英文关键词:Restenosis  Remodeling  MMP-2  MMP-9  TIMP-1
基金项目:
作者单位
葛夕洪 天津医科大学附属一中心临床学院放射科,300192 
杨晶 天津医科大学病理学教研室,天津 300070 
徐锐 天津医科大学总医院放射科,天津 300052 
王永利 天津医科大学总医院放射科,天津 300052 
司同国 天津医科大学总医院放射科,天津 300052 
贺能树 天津医科大学总医院放射科,天津 300052 
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中文摘要:
      目的 观察PTA后MMP-2、MMP-9和TIMP-1在血管壁各层随时间的演变规律,探讨其在血管再狭窄过程中的表达及意义。 方法 48只大鼠制作成颈动脉再狭窄动物模型,选取30只内膜增生满意的标本,分别代表动脉损伤后1、3、7、14、28、42天6个观察时间点,对胶原纤维进行Masson染色。MMP-2、TIMP-1、PCNA进行免疫组织化学染色,MMP-9进行免疫组织化学和原位杂交两种染色。分析它们的表达与内膜增生和血管重塑的关系。 结果 正常血管不表达MMP-9 mRNA及蛋白,损伤后第3天中膜、外膜mRNA表达达高峰,第7天内膜表达达高峰。MMP-9蛋白第7天内膜表达达高峰,且阳性细胞率高于中膜和外膜。第14、28天,血管壁各层表达逐渐下降至基线水平,内膜的阳性细胞主要集中在新生内膜靠近管腔的一侧。内膜MMP-2表达高峰出现晚至第14天,且近内弹力板处MMP-2也有明显的表达。正常血管壁不表达TIMP-1,损伤后第3天,中膜和外膜表达达高峰。第7天,新生内膜表达达高峰,中膜和外膜仍有较高水平表达。结论 MMP-9、MMP-2、TIMP-1参与再狭窄,内膜MMP-9表达与早期增殖的细胞向内膜迁移形成新生内膜有关。MMP-2表达与晚期内膜形成、内膜重塑有关。TIMP-1的表达对内膜增生和重塑没有直接作用,其表达升高是机体为适应MMPs升高做出的代偿反应,在维持自身平衡中起作用。
英文摘要:
      Objective To investigate the dynamic changes of MMP-2, MMP-9 and TIMP-1 in each layer of the artery wall, thus to conclude their expression and significance in restenosis procedures. Methods Common carotid artery injury model were created in 48 male SD rats. Only 30 rats were used because their neointima was good. Specimens were harvested at six time points that was 1st, 3rd, 7th, 14th, 28th and 42nd days. Masson trichrome stain was used to measure collagen content. PCNA, MMP-2 and TIMP-1 were stained with immunohistochemistry (IHC). MMP-9 was stained with both IHC and in situ hybridization (ISH). Then the relationgship between them and neointima formation and remodeling were analyzed. Results MMP-9 mRNA and protein did not express in normal artery wall. At the first day after injury, their mRNA expression presented in the media and adventia, peaked at 3rd days in adventia and media but at 7th days in the neointima, then decreased stepwise. MMP-9 protein peaked at 14th and 28th days, dropped gradually to baseline, the positive cells located mainly in the surface side of the lumen. MMP-2 expression peaked in the neointima delayed to 14th days, and could also be seen nearby the internal elastic lamina. TIMP-1 protein did not express in normal artery wall, it peaked at 3rd days in adventia and media but at 7th days in the neointima. The expression tendency of TIMP-1 was similar to that of PCNALI and had positive correlation with it. Conclusion MMP-9, MMP-2 and TIMP-1 has relation with restenosis. MMP-9 expresses in the neointima involves in the migration of proliferated cells to the formation of neointima during the early phase. MMP-2 expression involves the formation and remodeling of neointima during late phase. TIMP-1 expression is perhaps a compensation for the increased expression of MMPs and may plays a role in homeostasis.
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