阿司匹林和氯吡格雷抑制兔粥样硬化主动脉基质金属蛋白酶1的表达

目的研究抗血小板药物阿司匹林、氯吡格雷及两药合用对兔粥样硬化主动脉基质金属蛋白酶1表达和斑块稳定性的影响。方法49只雄性日本大耳白兔随机分为正常对照组、模型组、阿司匹林组、氯吡格雷组及合用组。后四组建立高胆固醇饲料和免疫损伤诱发的主动脉粥样硬化模型。免疫组织化学法测定斑块部位的巨噬细胞和平滑肌细胞阳性百分率并确定基质金属蛋白酶1在动脉壁的分布,Western印迹法测定主动脉基质金属蛋白酶1的表达水平。结果阿司匹林和氯吡格雷均明显减少巨噬细胞阳性百分率、增加平滑肌细胞阳性百分率(P<0.01),斑块中巨噬细胞部位与基质金属蛋白酶1阳性区域存在定位上的对应关系。模型组、阿司匹林组、氯吡格雷组、合用组主动脉基质金属蛋白酶1的表达分别是正常对照组的562%、217%、211%和178%,与模型组相比,阿司匹林组、氯吡格雷组及合用组基质金属蛋白酶1蛋白表达均显著降低(P<0.05)。结论氯吡格雷和阿司匹林能抑制动脉粥样硬化斑块内巨噬细胞表达基质金属蛋白酶1,并通过改变斑块组成对稳定斑块起作用。

Aspirin and Clopidogrel Reducing Matrix Metalloproteinase-1 Expression in Aortic Artery of Atherosclerostic Rabbits

Aim To study the effects of aspirin and clopidogrel on expression of matrix metalloproteinase-1(MMP-1) and stability of plaque in aortic artery of atherosclerostic rabbits. Methods Forty-nine rabbits were divided into normal control group,model group,aspirin group,clopidogrel group and combination(aspirin clopidogrel) group.Atherosclerostic model in aortic artery induced by high lipid diet chow and immunity injury were built in the last four groups.The positive percentage of macrophage cells and smooth muscle cells in the plaque were analyzed by immunohistochemistry.Expression of MMP-1 in aortic artery was measured by Western blot. Results Aspirin and clopidogrel significantly decreased the positive percentage of macrophage cells,and increased the positive percentage of smooth muscle cells in aortic vascular lesions(P<0.05 or 0.01).The localization of the expression of MMP-1 was in concordance with macrophage cells region.Compared with normal controls,the amounts of MMP-1 increased by 562%,217%,211% and 178% in model group,aspirin group,clopidogrel group and their combination,respectively(P<0.05). Conclusions Aspirin and clopidogrel can reduce expression of MMP-1 and change the compounds of plaques.These effects may increase the stability of plaques.