论文部分内容阅读
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。
Objective To investigate the effect of atorvastatin on the expression and activity of matrix metalloproteinase (MMP) 2 and MMP9 in rabbit abdominal aortic atherosclerotic plaque. Methods Twenty-eight male New Zealand white rabbits with a body weight of 2 kg were randomly divided into control group and hypercholesterolemia group. The latter group received abdominal aorta balloon injury after 2 weeks of feeding high cholesterol diet, and then randomly divided into model group and Atorvastatin group (given atorvastatin 5 mg · kg-1 · d-1) in each group 6, two groups were fed high-cholesterol diet for 4 weeks. Immunohistochemistry, gelatin zymography and reverse transcriptase polymerase chain reaction (RT-PCR) were used to detect the expression and activity of MMP2 and MMP9 in atherosclerotic plaque. Results The intima-media thickness of atorvastatin group was significantly thinner than that of model group [(0.49 ± 0.072 vs 0.66 ± 0.08) mm, P <0.05), and The number of foam cells was significantly reduced compared with model group. The immunohistochemical results showed that the expression of MMP2 in atorvastatin group was significantly lower than that in model group, and the mRNA expression of MMPs / GAPDH in atorvastatin group Which was significantly lower than that of the model group (MMP2 (3.58 ± 0.62 vs. 12.74 ± 1.01) and MMP9 (4.4 ± 1.07 vs. 10.21 ± 4.32, P < 0.05). Gelatin zymography showed that the activity of MMP9 and MMP2 in atorvastatin group was significantly lower than that in model group (40535 ± 7841 vs 57345 ± 9320 du / mg and (55744 ± 3430 ) To (80888 ± 5435) du / mg, all P <0.05. Conclusions Atorvastatin can inhibit the formation of atherosclerotic lesions by inhibiting the expression and activity of MMP2 and MMP9 in atherosclerotic plaques and stabilizing plaque.