瑞舒伐他汀对兔动脉粥样硬化斑块内CD147的表达及斑块稳定性的影响  

Effect of rosuvatation on the stability of the plaque and expression of CD147 in atherosclerotic plaques of rabbits

作　　者：薛峰[1] 杜大勇[2] 李运田[2] 李雪杰[2] 赖晓辉[2] 柳杨[2] 王新亮[2] 李沫言[2] 

机构地区：[1]南方医科大学心内科,广州510515 [2]解放军第305医院心脏疾病诊疗中心

出　　处：《山西医科大学学报》2013年第4期258-262,共5页Journal of Shanxi Medical University

基　　金：全军"十一五"医药卫生科研基金资助项目(06G145)

摘　　要：目的探讨瑞舒伐他汀对兔颈动脉粥样硬化斑块内的CD147表达水平、外周血清金属基质蛋白酶-2(MMP-2)、金属基质蛋白酶-9(MMP-9)的浓度水平以及斑块稳定性的影响。方法 18只新西兰大白兔随机分为三组:空白对照组、模型组(液氮损伤+高脂饲料建立动脉硬化模型)、药物干预组(造模后予以瑞舒伐他汀干预),分别测定兔外周血清MMP-2、MMP-9的浓度水平,15周后对兔颈总动脉血管进行病理形态学检查,逆转录聚合酶链反应(RT-PCR)检测斑块内CD147 mRNA表达水平,蛋白质印迹法(Western blot)检测斑块内CD147蛋白表达水平。结果第15周末,模型组外周血清MMP-2、MMP-9浓度水平、斑块内CD147 mRNA和蛋白表达水平均明显高于空白对照组(P<0.05)。病理显示模型组颈动脉内可见大量的不稳定斑块,模型组的6只兔中4只出现明显斑块破裂及血栓形成,而空白对照组的6只兔血管内膜光滑。药物干预组外周血清MMP-2、MMP-9浓度水平,斑块内CD147 mRNA和蛋白表达水平与模型组相比明显降低(P<0.05)。病理显示药物干预组颈动脉可见稳定斑块,未见斑块破裂。结论兔颈动脉不稳定斑块内CD147的表达增多,外周血清MMP-2、MMP-9的浓度水平明显升高;瑞舒伐他汀可能通过抑制CD147表达及抑制MMP-2、MMP-9的浓度水平,从而发挥其稳定动脉硬化斑块的作用。Objective To elucidate the impact of rosuvatation on the stability and expression of matrix matalloproteinase-2 （ MMP-2）, matrix matalloproteinase-9（ MMP-9）, CD147 in atherosclerotic plaques of rabbits. Methods Eighteen New Zealand white male rab- bits were randomly divided into three groups ： blank control group （ n = 6）, model group （ n = 6 ） and drug intervention group （ n = 6 ）. Rabbits were fed with high fat diet to induce the atherosclerosis model after giving the liquid nitrogen via right common carotid artery. Rosuvatation was gavaged after the modeling. The carotid arteries in all groups were collected to undergo the pathological examination. The expression of MMP-2 and MMP-9 were detected at baseline and at week 15. The CD147 mRNA and protein expression was respec- tively detected by RT-PCR and Western blot at week 15. Results Compared with blank control group,the expression levels of MMP- 2, MMP-9, CD147 mRNA and CD147 protein in model group significantly increased（ P 〈 0.05 ）, and the plaques were also more unsta- ble. The plaque disruption and thrombosis occurred in 4 out of 6 rabbits in model group. Compared with model group, the expression lev- els of MMP-2, MMP-9, CD147 mRNA and CD147 protein in drug intervention group significantly decreased （ P 〈 0.05 ）, and the plaques were stable in drug intervention group. Conclusion The expression of CD147 ,MMP-2 and MMP-9 will significantly increase in unsta- ble plaques and rosuvatation can stabilize them by inhibiting CD147, MMP-2 and MMP-9 expression.

关 键 词：动脉粥样硬化 瑞舒伐他汀 CD147 基质金属蛋白酶-2 基质金属蛋白酶-9 兔 

分 类 号：R543.5[医药卫生—心血管疾病]