阿托伐他汀对兔动脉粥样硬化斑块近心端基质金属蛋白酶9表达的影响  

Effect of atorvastatin on matrix metalloproteinase 9 expression in the upstream shoulder of aortic atherosclerotic plaques in rabbits

作　　者：刘德志[1] 葛颂[1] 周广怡[1] 胡伟[1] 徐格林[1] 张仁良[1] 刘新峰[1] 

机构地区：[1]南京大学医学院临床学院南京军区南京总医院神经内科,210002

出　　处：《中国脑血管病杂志》2008年第8期359-363,共5页Chinese Journal of Cerebrovascular Diseases

基　　金：江苏省"六大人才高峰"第三批资助项目(06-B-075)

摘　　要：目的研究阿托伐他汀对兔主动脉粥样硬化斑块近心端基质金属蛋白酶9(MMP-9)表达的影响。方法将30只雄性新西兰大白兔随机分为正常对照组(9只)、高脂饮食组(11只)、阿托伐他汀组(10只)。后两组给予高胆固醇饲料建立主动脉粥样硬化模型,至第9周始,高脂饮食组同时服用1.5mg.kg-1.d-1淀粉,阿托伐他汀组服用阿托伐他汀1.5mg.kg-1.d-1。处死兔后,对主动脉大体标本进行观察,发现内膜增生合并粥样斑块形成者视为模型建立成功。应用免疫组化法测定斑块近心端的巨噬细胞和平滑肌细胞阳性面积百分率以及MMP-9的表达。结果①高脂饮食组和阿托伐他汀组主动脉可见新生内膜形成,内-中膜厚度比值分别为1.41±0.34、0.63±0.12。②斑块中巨噬细胞分布部位正是MMP-9阳性表达区域,均聚集于斑块近心端。高脂饮食组和阿托伐他汀组主动脉斑块近心端巨噬细胞阳性面积百分比分别为(26.5±4.3)%、(12.4±1.5)%,MMP-9吸光度(A值)分别为0.081±0.014、0.022±0.004,两组比较差异均有统计学意义(P<0.01)。③高脂饮食组与阿托伐他汀组平滑肌细胞阳性面积百分比分别为(47.2±12.3)%、(50.4±10.8)%,差异无统计学意义(P>0.05)。结论动脉粥样硬化斑块内巨噬细胞及MMP-9表达主要位于主动脉粥样硬化斑块近心端,阿托伐他汀能显著减少此区域巨噬细胞聚集及MMP-9的表达。Objective To study the effect of atorvastatin on matrix metalloproteinase 9 （MMP-9） expression in the upstream shoulder （proximal end ） of aortic atherosclerotic plaques in rabbits. Methods Thirty male New Zealand rabbits were randomized into normal control group（ n = 9） , high-lipid diet group（n = 11 ） and atorvastatin group（n = 10）. An aortic atherosclerotic model was induced by high- lipid diet in the last two groups. From the ninth week, the high-lipid diet group rabbits were administered starch 1.5 mg/kg body weight per day, and the rabbits of atorvastatin group were administered atorvastatin 1.5 mg/kg body weight per day. After the rabbits were killed, the gross specimen of aorta was observed, and the rabbits whose intimal hyperplasia complicated with the formation of atherosclerotic plaque were regarded as the successful induction of the model. The percentage of macrophage and smooth muscle cell positive area in the upstream shoulder of plaques and the expression of MMP-9 were detected by immunohistochemistry methods. Results The formation of neointima was seen in aorta in the high-lipid diet and atorvastation groups, the ratios of intima-media thickness were 1.41 ± 0. 34 and 0. 63 ± 0. 12, respectively. The distribution sites of macrophages in the plaques were in concordance with the region of positive expression of MMP-9, and they were all assembled at the upstream shoulder of the plaques. As compared with the high-lipid diet group, atorvastatin reduced aggregation of macrophages significantly （ the percentages of positive areas were 26. 5% -4. 3% and 12. 4% - 1.5%, respectively） and expression of MMP-9 （ the values of optical density were 0. 081 -0. 014 and 0. 022 ±0. 004, respectively） in the upstream shoulders of the aortic plaques. There were significant differences between the two groups （ P 〈 0. 01 ）. The percentages of positive areas of smooth muscle cells in the high-lipid diet and atorvastatin groups were 47.2% - 12. 3% and 50. 4% - 10. 8%, respectively. Ther

关 键 词：动脉粥样硬化 明胶酶B 主动脉 兔 阿托伐他汀 

分 类 号：R543.1[医药卫生—心血管疾病]