罗格列酮对兔动脉粥样硬化MMP-2,TIMP-2表达的影响.doc

罗格列酮对兔动脉粥样硬化MMP-2、TIMP-2表达的影响﹡ 李万玲1，贾军正1，郭文芬1，王志禄2△，张丽1，崔丽君1，谈丽丽1，王锋1，徐芳1， 蒙颖1 (730000兰州，兰州大学：第一临床医学院1，第一医院心内科2) [摘要] 目的 通过比较罗格列酮和辛伐他汀对兔动脉粥样硬化MMP-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(HTL)及高脂饲养结合的方法建立兔动脉粥样硬化模型。ELISA法和免疫组化法分别用于检测血清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(P＜0.05)；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(P＜0.05)，血清ox-LDL、sCD40L水平显著降低(P＜0.01)；辛伐他汀组和罗格列酮组比较，差异无统计学意义(P＞0.05)。结论 罗格列酮可通过下调兔主动脉粥样硬化组织中MMP-2及上调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从而发挥抗动脉粥样硬化作用。 [关键词] 罗格列酮；辛伐他汀；动脉粥样硬化；基质金属蛋白酶-2； [中图法分类号] R541.6；R363.27；R977 [文献标志码] A Effects of Rosiglitazone on MMP-2 and TIMP-2 Expression in Atherosclerotic Rabbits LI Wanling1, JIA Jun-zheng1, GUO Wen-fen1, WANG Zhi-lu2, ZHANG Li1, CUI Li-jun1, TAN Li-li1, WANG Feng1, XU Fang1, MENG Ying1 (1First Clinical Medical College of Lanzhou University, 2Department of Cardiology, First Hospital of Lanzhou University, Lanzhou, Gansu Province, 730000, China) [基金项目] [基金项目] 甘肃省自然科学研究基金资助(1010RJZA122)，甘肃省卫生行业科研计划管理项目(GWGL2010-16) [通信作者] 王志禄，E-mail:wangzhilu@ [Abstract] Objective Comparison the effect of rosiglitazone and simvastatin on the expression of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinase (TIMP)-2 in atherosclerotic rabbits model and to explore the anti-atherosclerotic mechanisms. Methods 36 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 used to reproduce atherosclerotic rabbit model. Enzyme-linked immuno sorbent assay (ELISA) and immunohistochemistry staining were performed to detect the serum levels of ox-LDL and sCD40L, MMP-2 and TIMP-2 protein expression respectively. Results Compared with the control group, the MMP-2 expression were significantly increased and the TIMP-2 expression were significantly decrease