【摘要】 目的探讨阿托伐他汀对家兔腹主动脉粥样硬化斑块基质金属蛋白酶(MMP)2和MMP9表达及活性的影响。方法18只体重2kg左右雄性新西兰兔随机分为对照组和高胆固醇血症组,后者喂饲高胆固醇饲料2周后行腹主动脉内膜球囊拉伤术,术后再随机分为模型组和阿托伐他汀组(给予阿托伐他汀5 mg·kg-1·d-1)每组6只,两组均继续喂饲高胆固醇饲料4周。采用免疫组化、明胶酶谱法和逆转录多聚酶链反应(RT-PCR)检测腹主动脉粥样硬化斑块MMP2和MMP9的表达及活性。结果阿托伐他汀组的腹主动脉内膜厚度较模型组显著减薄[(0．49±0．072)对(0．66±0．08)mm,P<0．05)],并且泡沫细胞的数量较模型组显著减少;免疫组化检测结果示阿托伐他汀组血管壁中MMP2的表达量显著较模型组减少;RT-PCR提示阿托伐他汀组的MMPs／GAPDH的mRNA表达较模型组显著降低,分别为MMP2(3．58±0．62对12．74±1．01)和MMP9(4．4±1．07对10．21±4．32),均为P<0．05;明胶酶谱法显示,阿托伐他汀组血管壁MMP9和MMP2的活性亦较模型组显著降低,分别为(40535±7841)对(57345±9320)du／mg和(55744±3430)对(80888±5435)du／mg,均为P<0．05。结论阿托伐他汀可能通过抑制动脉粥样硬化斑块内MMP2和MMP9的表达和活性,而抑制动脉粥样硬化病变的形成,起到稳定斑块的作用。更多还原

【Abstract】 Objective To investigate the effect of atorvastatin on the expression and activity of matrix metalloproteinases (MMPs) in rabbit abdominal arterial atherosclerotic plaque. Methods Eighteen male New Zealand rabbits weighing 2 kg were randomized to normal control group (n=6) and hypercholesterolemia group (n=12). The latter was given hypercholesterol diet for 2 weeks, and then catheter-induced abdominal aortic wall injury was performed. Rabbits in hypercholesterolemia and aortic injury group were randomized to model group (n=6,4 weeks of hypercholesterol diet) and atorvastatin(5 mg·kg-1·d-1 for 4 weeks)group (n=6). Finally, the levels of MMP2 and MMP9 protein and mRNA in the abdominal aortic artery were measured by immunohistochemical analysis, reverse transcription-polymerase chain reaction (RT-PCR), sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) zymography. Results The intimal-medial thickness[(0. 49±0. 072) mm vs (0.66±0.079) mm, P < 0. 05] in atorvastatin group was significantly less than in hypercholesterolemia model group. There were much less foam cells present in atherosclerotic plaque in atorvastatin group. Immunohistochemical analysis showed much less stain in MMP2 in atorvastatin group than in hypercholesterolemia model group. The mRNA expressions of MMP2 (3. 58±0. 62 vs 12. 74±1. 01, P<0.05) and MMP9 (4. 4±1.07 vs 10.21±4. 32, P<0.05) were significantly decreased in atorvastatin group. The activity of MMP9 [(40535±7811)vs(57345±9320 )du/mg , P <0. 05)]and MMP2 [(55744±3430)vs(80888±5435 )du/mg,P<0. 05)] were significantly lower in atorvastatin group than in hypercholesterolemia model group. Conclusions Atorvastatin may decrease the expressions and activities of MMP2 and MMP9 in atherosclerotic plaque, and inhibit the development of foam cells, thereby prohibit the formation and development of atherosclerosis.更多还原