小剂量阿司匹林对动脉粥样硬化兔主动脉MMP-2表达的影响

Effect of low dose aspirin on the expression of MMP-2 in the aorta of atherosclerotic rabbit

目的评估小剂量阿司匹林对动脉粥样硬化兔主动脉基质金属蛋白酶-2(MMP-2)的表达及动脉硬化严重程度的影响。方法 24只雄性新西兰兔随机分为对照组(喂食普通兔料)、模型组(喂食高脂饲料)、阿司匹林组(喂食高脂饲料并给予小剂量阿司匹林干预),每组8只。饲养12周后处死动物,取主动脉进行病理学检查,分别应用RT-PCR和Western-bolt分析主动脉病灶中MMP-2 mRNA和蛋白的表达。结果病理学大体观察发现,对照组无动脉粥样硬化斑块形成,模型组和阿司匹林组主动脉斑块最大厚度、平均斑块厚度、管腔狭窄度和斑块所占周径比值等4项指标两两比较均有显著性差异(P<0.01)。对照组中MMP-2蛋白和mRNA呈低水平表达,而在模型组中的表达均明显增高,阿司匹林组MMP-2蛋白和mRNA的表达降低(P均<0.01)。结论 MMP-2在正常血管组织中低水平表达,随血管动脉粥样硬化程度的加重而升高;小剂量阿司匹林可以有效地减少动脉粥样硬化兔主动脉MMP-2表达,减轻动脉硬化的严重程度。

Objective To evaluate the effect of low dose aspirin on the severity of atherosclerosis and the expression of metalloproteinase-2（MMP-2） in the aorta of atherosclerotic rabbit.Methods 24 male New Zealand rabbits were randomly divided into control group（normal rabbit diet）,model group（high cholesterol diet）,aspirin group（high cholesterol diet and low dose aspirin ）,8 rabbits in each group.After 12 weeks,animals were killed,and the aorta were obtained for pathological examination.RT-PCR and Western blot were used to analyze MMP-2 mRNA and protein expression respectively.Results The maximal plaque thickness,average plaque thickness,degree of aortic luminal stenosis and the ratio between plaque and lumen circumference in 3 groups were significantly different from each other（P0.01）.The expressions of MMP-2 protein and mRNA in atherosclerotic groups were significantly higher than that in normal control group;but the expressions of MMP-2 protein and mRNA were reduced respectively（P0.01 ） in the low dose aspirin group compared with the model group.Conclusion The expression of MMP-2 is low in normal vascular and gradually increased with the severity degree of atherosclerosis.Low dose aspirin can significantly reduce the expression of MMP-2 and the severity of atherosclerosis.