Objective:To explore the anti-atherosclerotic mechanism of rosiglitazone by comparing the effects of rosiglitazone and simvastatin on the expressions of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinase (TIMP)-2 in atherosclerotic rabbit model. Methods: Thirty-six male New Zealand rabbits were randomly divided into control group.model group, simvastatin group and rosiglitazone group. Subcutaneous injection of dl-homocysteine thiolactone (HTL) with high fat feeding was conducted to reproduce atherosclerotic rabbit model. Enzyme-linked immunosorbent assay (ELISA). and immunohistochemistry staining were performed to detect the serum levels of ox-LDL and sCD4UL, and MMP-2 and TIMP-2 protein expressions, respectively. Results:Compared with the control group, the MMP-2 expression was significantly increased and the TIMP-2 expression was significantly decreased in the other three groups (P<0. 05). Compared with the model group, the expressions of MMP-2 protein in the simvastatin group and the rosiglitazone group were decreased significantly, but the expressions of TIMP-2 protein were increased significantly (P<0. 05)s serum levels of ox-LDL and sCD40L were decreased significantly. However, the parameters mentioned above were similar between simvastatin group and rosiglitazone group (P>0. 05). Conclusion: Rosiglitazone could downregulate the expression of MMP-2 and upregulate the expression of TIMP-2, reduce serum levels of ox-LDL and sCD40L, and alleviate the inflammatory reaction associated with atherosclerosis.%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,TIMP2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.
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