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目的:通过比较罗格列酮和辛伐他汀对兔动脉粥样硬化基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制因子-2(TIMP-2)表达的影响,探讨罗格列酮抗动脉粥样硬化的作用机制。方法:将36只雄性新西兰兔随机分为对照组、模型组、辛伐他汀组和罗格列酮组;采用皮下注射同型半胱氨酸硫内酯及高脂饲养的方法建立兔动脉粥样硬化模型。检测血清氧化低密度脂蛋白(ox-LDL)、sCD40L水平和主动脉粥样硬化组织中MMP-2和TIMP-2的表达。结果:与对照组相比,其他3组MMP-2蛋白表达显著升高,而TIMP-2蛋白表达显著降低;与模型组比较,辛伐他汀和罗格列酮组MMP-2表达显著降低,TIMP-2表达显著增加,血清ox-LDL、sCD40L水平显著降低。辛伐他汀组和罗格列酮组比较,差异无统计学意义。结论:罗格列酮可通过下调兔主动脉粥样硬化组织中MMP-2、上调TIMP-2的表达,降低血清ox-LDL和sCD40L水平,减轻大动脉内膜的炎性反应,发挥抗动脉粥样硬化的作用。
Objective: To investigate the effects of rosiglitazone and simvastatin on the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-2 (TIMP-2) Anti-atherosclerosis mechanism of action. Methods: Thirty-six male New Zealand white rabbits were randomly divided into control group, model group, simvastatin group and rosiglitazone group. Rabbit atherosclerosis was induced by subcutaneous injection of homocysteine and lactose Hardening model. The levels of serum oxidized low density lipoprotein (ox-LDL), sCD40L and the expression of MMP-2 and TIMP-2 in aortic atherosclerosis were detected. Results: Compared with the control group, the expression of MMP-2 in the other three groups was significantly increased and the expression of TIMP-2 protein was significantly decreased. Compared with the model group, MMP-2 expression was significantly decreased in simvastatin and rosiglitazone groups, TIMP-2 expression was significantly increased serum ox-LDL, sCD40L levels were significantly lower. Simvastatin group and rosiglitazone group, the difference was not statistically significant. CONCLUSION: Rosiglitazone can decrease the level of serum ox-LDL and sCD40L, decrease the inflammatory reaction of the intima of the aorta by down-regulating MMP-2, up-regulating the expression of TIMP-2 in aortic atherosclerosis, Like the role of sclerosis.