颈动脉粥样硬化斑块CD147、MMP-9表达及阿托伐他汀干预的影响  

Expressions of CD147, matrix metalloproteinase-9 in carotid atherosclerotic plaque and the interference effect of atorvastatin on them

作　　者：高菊华[1] 高小平[1] 

机构地区：[1]湖南师范大学第一附属医院,湖南省人民医院神经内科,长沙410005

出　　处：《中华神经医学杂志》2010年第11期1081-1085,共5页Chinese Journal of Neuromedicine

基　　金：湖南省卫生厅科研课题计划项目（B2009076）

摘　　要：目的 探讨兔颈动脉粥样硬化斑块中CD147、基质金属蛋白酶-9（MMP-9）的表达情况以及阿托伐他汀对其表达的影响.方法 24只新西兰大白兔按随机数字表法分为3组：正常对照组8只,普通饲料喂养16周;余16只给予球囊损伤颈总动脉＋高胆固醇喂养,12周后分成模型对照组和阿托伐他汀组（每天2.5 mg/kg阿托伐他汀灌胃）,继续喂养4周后给予鲁塞尔氏蛙蛇毒和组胺触发斑块破裂.对斑块进行病理分析,免疫组织化学法检测斑块内巨噬细胞及CD147、MMP-9蛋白表达,逆转录聚合酶链反应（RT-PCR）检测斑块内CD147、MMP-9mRNA表达.结果 药物触发后模型对照组存活的6只兔中有4只发生斑块破裂及血栓形成,阿托伐他汀组存活的7只兔中有1只发生斑块破裂及血栓形成,正常对照组中未见斑块破裂及血栓形成.与模型对照组比较,阿托伐他汀组斑块内巨噬细胞含量明显减少（33.62±3.82vs16.22±2.61）,CD147蛋白表达的阳性染色面积比明显降低（29.54±3.03vs14.22±1.63）,MMP-9蛋白表达的阳性染色面积比明显降低（21.18±4.75 vs 11.11±1.87）,差异有统计学意义（P＜0.05＝.模型对照组和阿托伐他汀组斑块内CD147 mRNA表达水平分别为0.939±0.105和0.426±0.112,MMP-9 mRNA表达水平分别为0.335±0.069和0.135±0.067,比较差异有统计学意义（P＜0.05＝.Pearson相关检验显示斑块中MMP-9蛋白与CD147蛋白表达呈正相关（r=0.669,P=0.001）,MMP-9 mRNA与CD147 mRNA表达呈强正相关（r=0.783,P=0.000）.结论 CD147、MMP-9表达上调可能参与斑块不稳定的发生机制,阿托伐他汀可能通过下调CD147、MMP-9的表达发挥稳定斑块的作用.Objective To investigate the expression of CD147 and matrix metalloproteinase-9 （MMP-9） in rabbit models of carotid atherosclerotic plaque and the interference effect of atorvastatin on their expressions. Methods Twenty-four New Zealand white male rabbits were randomly divided into group A （normal diet group, n=8）, and group B （n=16）. Group A was given normal diet for 16 weeks. The 16 rabbits in group B underwent balloon-induced endothelial injury in the right carotid artery, and thereafter, were fed with a high-cholesterol diet （1% cholesterol） for 12 weeks; then, these rabbits were divided into group C （the model control group）, and group D （undergoing gastric perfusion of atorvastatin Russell＇s viper venom and histamine. The damaged carotid arteries in all the groups were collected to undergo pathological examination. The protein expressions of MMP-9 and CD147, and the level of macrophages were detected by immunohistochemical analysis, and the mRNA expressions of MMP-9 and CD147 were evaluated by reverse-transcription PCR. Results In group C, it was found that plaque disruption and thrombosis occurred in 4 out of the 6 rabbits after triggering, while in group D, only 1 rabbit demonstrated plaque disruption and thrombosis; however, rabbits in the normal diet group did not have plaque disruption and thrombosis. Group D showed significantly decreased level of macrophage （16.22±2.61）, decreased percentages of positive staining area of protein expression levels of MMP-9 （11.11±1.87） and CD147 （14.22±1.63） as compared with group C （33.62±3.82, 21.18±4.75 and 29.54±3.03, respectively） （P〈0.05）. Significant difference on the mRNA expression levels of CD147 and MMP-9 was noted between group C （0.939±0.105, 0.335±0.069, respectively） and group D （0.4256±0.112, 0.135 ±0.067, respectively） （P〈0.05）. The levels of the protein, mRNA expressions of CD 147 and MMP-9 were correlative positively by Pearson＇s correlation coefficient （r=0.669, 0.783, respec

关 键 词：动脉粥样硬化 CD147 基质金属蛋白酶-9 阿托伐他汀 

分 类 号：R686[医药卫生—骨科学]