家兔不同类型颈动脉斑块中基质金属蛋白酶-2表达的形态学研究

Morphological study on the expression of MMP-2 in different types of carotid plaques of rabbits

目的建立不同类型颈动脉斑块的动物模型,比较不同斑块内基质金属蛋白酶-2 (MMP-21的阳性表达,观察MMP-2与斑块易损性的关系。方法将动物随机分为高脂饲料(加或不加蛋氨酸)喂养组(B/A组),再以加或不加内膜空气干燥法分为B1、A1/B2、A2组,建立不同类型的颈动脉粥样硬化斑块的动物模型:免疫组化观察斑块内MMP-2表达,并进行纤维帽厚度/脂质核比值及免疫灰度测定。结果(1)病变管腔偏心性狭窄,呈不规则裂隙状;内膜不均匀增厚;中膜变薄;内、中膜大部分离。可见泡沫细胞的典型聚集形态和典型的纤维帽形态。(2)斑块易损性分析,依次是B1>A1>B2>A2(P<0.01)。(3)颈动脉斑块内MMP-2的阳性表达与斑块易损性呈正相关,免疫灰度依次是B1>A1>B2>A2(P<0.01)。结论(1)采用高脂饲料加空气干燥法能成功建立颈动脉斑块的动物模型。(2)MMP-2的阳性表达与斑块的易损性呈正相关,MMP-2阳性表达结合纤维帽厚度/脂质核比值来判断颈动脉斑块易损性的方法能为研究斑块易损性提供一个有意义的标准。

Objective To establish animal models with carotid plaques of different types, and further investigate the correlation between matrix metalloproteinase-2 （MMP-2） and carotid plaque vulnerability through the comparison between positive expressions of MMP-2 in different plaques. Methods Animal models with different types of carotid atherosclerotic plaques were established by high cholesterol （with or without methionine） diet（Group B, A） plus air-drying（Group B1, A1）, group B and A without air-drying were assigned into group B2 and A2. Immunohistochemical techniques were applied to observe the expression of MMP-2 in the plaques and the ratio between the fiber cap thickness and lipid core and immunity grayscale were determined. Results （1）. Eccentric stenosis occurred to the lumina with pathological changes, irregularly slit-shaped; the tunica intima was unevenly thickened; the tunica media was thinned; the tunica intima and media were largely isolated. Typical aggregation morphology of foam cells and typical morphology of fiber cap were observed. （2）. Plaque vulnerability analysis showed that, B1 〉A1 〉B2〉A2 （P〈0.01）, in turn. （3）. The positive expression of MMP-2 in carotid plaques was positively correlated with plaque vulnerability and the immunity grayscale was BI〉AI〉B2〉A2 （P〈0.01） in turn. Conclusion （1）. Animal models with carotid plaques of various types can be successfully established with high cholesterol diet plus air-drying. （2）. The positive expression of MMP-2 is positively correlated with plaque vulnerability and the positive expression of MMP-2 coupled with the ratio between the fiber cap thickness and lipid core may provide a standard of much sense for determining plaque vulnerability in future.