基质金属蛋白酶抑制剂对兔动脉粥样硬化斑块的影响

Effects of Matrix Metalloproteinase Inhibitor on Stabilization of Atherosclerotic Plaque

目的:观察基质金属蛋白酶抑制剂四环素对兔动脉粥样硬化组织中基质金属蛋白酶-2(Matrix Metalloproteinase-2,MMP-2)活性和表达的影响,探讨其对动脉粥样硬化斑块稳定性的作用。方法:30只雄性新西兰白兔随机分为3组,正常组(n =10)喂正常饲料;模型组(n=10)喂高胆固醇饲料;四环素组(n=10)喂高胆固醇饲料,同时给予四环素250mg·d^(-1)·只^(-1)。饲养12w后处死.取出降主动脉分成两份。一份用于HE常规染色和Masson's染色后进行病理形态学观察和MMP-2免疫组化检查。另一份,用酶谱法(SDS-PAGE电泳)测定MMP-2酶活性。采用Mivnt图像分析软件对病理图像及电泳凝胶消化条带进行分析。结果:模型组和四环素组动脉内膜厚度比正常组明显增厚(P<0.01);模型组和四环素组,动脉粥样硬化斑块组织中MMP-2的表达和活性明显高于正常组(P<0.01),四环素组比模型组明显减弱(P<0.01);动脉粥样硬化斑块的纤维帽厚度/脂质池厚度、纤维帽面积/脂质池面积的比值明显小于四环素组(P<0.01)。结论:动脉粥样硬化组织中MMP-2酶的表达和活性明显增高;四环素明显抑制MMP-2酶的活性和表达,增加动脉粥样硬化斑块纤维帽厚度/脂质池厚度和斑块纤维帽面积/脂质池面积的比值,增加动脉粥样硬化斑块的稳定性。

Objective ：To investigate the effects of tetracycline, a matrix metalloproteinase inhibitor on expression and activity of matrix metalloproteinase -2 in atherosclerotic arterial tissues of rabbits, and it＇s role in the stabilization of atherosclerotic plaque. Methods： 30 male New Zealand rabbits were randomly divided into 3 groups： control group （n = 10 ）, model group （n = 10 ） and tetracycline group （ n = 10 ）. The rabbits were fed on normal diet, cholesterol diet （ cholesterol, 1.0 g/d ;lard, 5.0 g/d, ） and cholesterol diet with tetracycline （cholesterol, 1.0 g/d;lard, 10 g/d; tetracycline, 0. 25 g/d per rabbit ） respectively for 12 weeks. Descending aortas of rabbits were harvested for immunocytochemical staining, HE staining and Masson＇ s staining, respectively. The activity of MMP -2 was measured by zemography. Results： the intimal thickness of artery in cholesterol and tetracycline group were increased significantly than those in control group（P 〈0. 01 ）. The activity and expression of MMP -2 in cholesterol and tetracycline group were increased significantly than that of in control group（ P 〈 0.01 ）and was decreased significantly in tetracycline group than in cholesterol groups（ P 〈 0. 01 ）. the ratio of thickness and area of plaque fibrocap to that of lipid pool was increased significantly in tetracycline group than that of in cholesterol group （ P 〈 0. 01 ）. Conclusion： The expression and activity of MMP - 2 in atherosclerotic plaque were increased significantly and were inhibited significantly by tetracycline. The ratio of thickness and area of plaque fibrocap to that of lipid pool was increased significantly in tetracycline group than that of in cholesterol group,this suggestive that tetracycline may enhance the stabilization of atherosclerotic plaque.