基质金属蛋白酶9及转化生长因子β1在人动脉粥样硬化斑块的表达及其与斑块稳定性的关系

The Expression of Matrix Metalloproteinases-9, Transforming Growth Factor-Beta1 and Transforming Growth Factor-Beta ReceptorⅠin Human Atherosclerotic Plaque and their Relationship with Plaque Stability

目的探讨基质金属蛋白酶9、转化生长因子β1及转化生长因子β受体Ⅰ在人动脉粥样硬化粥样斑块中的表达水平,以及三者与粥样斑块稳定性的关系。方法收集人冠状动脉斑块组织共41例,常规石蜡包埋切片,作HE染色,根据镜下结构将斑块组织分为稳定组和不稳定组,采用免疫组织化学方法分析基质金属蛋白酶9、转化生长因子β1及转化生长因子β受体Ⅰ在人粥样斑块中的表达,并通过计算机图像分析系统进行定量。结果不稳定性斑块内,基质金属蛋白酶9的表达要明显强于稳定性斑块(面积密度为0.21±0.04比0.16±0.02,吸光度为3.48±0.65比2.84±0.27,P<0.01);转化生长因子β1则明显弱于稳定性斑块(面积密度为0.17±0.02比0.23±0.05,P<0.01;吸光度为3.16±0.65比3.60±0.55,P<0.05);两者在斑块内的表达呈明显的负相关(面积密度为r=-0.332,P=0.034;吸光度为r=-0.373,P=0.016),转化生长因子β受体Ⅰ的表达无明显差异。结论基质金属蛋白酶9、转化生长因子β1同斑块的稳定性密切相关,基质金属蛋白酶9是形成不稳定性斑块的重要促进因素,转化生长因子β1则是重要的斑块稳定因素。

Aim To investigate the expression of matrix metalloproteinases-9 （ MMP-9 ）, transforming growth factor-betal （TGF-β1） and TGF-beta receptor Ⅰ （TβR-Ⅰ ）in human atherosclerotic plaque and the relationship between them and plaque stability. Methods 41 specimen of human coronary artery atherosclerotic plaque were obtained from patients undergoing cardiovascular surgery, and then were routine paraffin embedded, sectioned at 4μm , and stained with hematoxylin and eosin. They were divided into stable （with no or only little lipid core） and unstable plaques （with lipid core size 〉 40% ） according to the structure under the opticalmicroscope, the qualitive and quantitive analyses of MMP-9, TGF-β1 and TβR- Ⅰ were performed by using immunohistochemical staining technique and auto picture analysis system. Results The immunopositive stain of MMP-9, TGF-β1 and TβR- Ⅰ were all located in the vascular smooth muscle cells, endothelial cells, fibroblast, and particularly in the foam cells and macrophage in the atherosclerotic plaque tissue. The protein expression of MMP-9 in the unstable plaques was much stronger than than in the stable ones （ average area density： 0.21 ± 0.04 vs 0.16 ± 0.02, average absorbent values： 3.48± 0.65 vs 2.84± 0.27, P 〈 0.01 ）, and was also stronger on the shoulder of the plaque, in the foam cells and macrophage around the lipid core, while the protein expression of TGF-β1 was much stronger in tile stable plaques （ average area density ： 0.23± 0.05 vs 0.17±0.02, P〈0.01; averageabsorhent values： 3.60±0.55vs3.16±0.65, P〈0.05）. There were no significant difference for immunopositive stain of TβR-Ⅰ between the stable and unstable plaques. Correlation analysis showed that there was a negative correlation between the expression of MMP-9 and TGF-β1 with both average area density and average absorbent values （ r =-0.332, P = 0.034 for average area density; r=-0.373, P=0.016 for average absorbent values）.Condusions There was a close relationship between MMP-9,TGF-β1 and plaque stability. Enhanced production MMP-9 may participate in the formation of unstable plaque, while TGF-β1 may be an important stabilizing factor to prevent the transition into an unstable plaque phenotype.