氯沙坦对动脉粥样硬化兔斑块稳定性的影响

山东大学学报(医学版)

氯沙坦对动脉粥样硬化兔斑块稳定性的影响

张永欢¹,杨彩云²,李师国²,李瑞峰¹,董波³

1. 山东大学医学院病理学与病理生理学研究所, 济南 250012;2. 济南历下区人民医院内科, 济南 250011; 3. 山东大学省立医院心内科, 济南 250021

收稿日期:2007-09-18 修回日期:1900-01-01 出版日期:2008-01-16 发布日期:2008-01-16
通讯作者: 李瑞峰

Effect of Losartan on the stability of atheromatous plaques in rabbits

ZHANG Yong-huan¹,YANG Cai-yun²,LI Shi-guo²,LI Rui-feng¹,Dong Bo³

1. Department of Pathology and Pathophysiology,School of Medicine, ShandongUniversity;2. Lixia Distric People′s Hospital of Jinan City;3. Department of Cadiology, Shandong Provincial Hospital, Shandong University

Received:2007-09-18 Revised:1900-01-01 Online:2008-01-16 Published:2008-01-16
Contact: LI Rui-feng

摘要/Abstract

摘要： 摘要：目的观察氯沙坦对动脉粥样硬化(AS)兔斑块中基质金属蛋白酶-3(MMP-3)、巨噬细胞数量的影响,探讨其稳定AS斑块的可能机制。方法应用球囊扩张腹主动脉加高脂饮食建立AS兔模型,将16只雄性新西兰大白兔随机分为2组,每组8只。模型组:饲喂含1％胆固醇高脂饲料;氯沙坦组:饲喂含1％胆固醇高脂饲料加氯沙坦25mg/(kg·d),连续用药4个月。免疫组化法检测AS斑块中MMP-3的蛋白表达水平及巨噬细胞在AS斑块中的阳性面积;电镜观察两组AS斑块超微结构变化;实时定量逆转录-聚合酶链反应(RT-PCR)检测AS斑块中MMP-3 mRNA的表达。结果免疫组化显示,氯沙坦组与模型组相比MMP3蛋白表达显著减少(P＜005),巨噬细胞在AS斑块中的数量明显降低(P＜0.05);MMP-3 mRNA的表达明显减少(P＜0.05)。结论氯沙坦可通过下调MMP.3的水平,减少斑块内巨噬细胞的数量来稳定AS斑块。

Abstract: To explore the effects of Losartan on the expression of matrix metalloproteinases-3(MMP-3) and the number of macrophages in rabbits with atherosclerotic plaque(AP) and to explore the mechanisms of increasing the stability of AP. MethodsThe experimental atherosclerotic models were induced by endothelial injures on the ventroaorta with a balloon and hyperlipid feeding for four months. Sixteen male New Zealand rabbits were randomly divided into two groups: the model group which was fed with standard diets containing 1％ cholesterol and the Losartan group which was fed with standard diets containing 1％ cholesterol and losartan 25mg／(kg·d). The proteinum expression of MMP-3 and the positive area of macrophage cells in the AP were determined by the immunohistochemistry technique. The structures of the AP of the two groups were observerd with an electron microscope. Realtime RTPCR was used to determine the mRNA expression of MMP-3. ResultsCompared with the model group, the proteinum expression of MMP3 and the number of macrophage cells in the Losartan group were significantly decreased(P＜0.05). The expression of MMP-3 mRNA was more significantly decreased in the Losartan group than that in the model group(P＜0.05). ConclusionLosartan may stabilize vulnerable plaque by suppressing the expression of MMP-3 and reducing the number of macrophage cells.

Key words: Losartan, Atherosclerosis, Matrix metalloproteinases-3, Macrophage

中图分类号:

R541-4

张永欢,杨彩云,李师国,李瑞峰,董波 . 氯沙坦对动脉粥样硬化兔斑块稳定性的影响[J]. 山东大学学报(医学版), 2008, 46(1): 64-67.

ZHANG Yong-huan,YANG Cai-yun,LI Shi-guo,LI Rui-feng,Dong Bo. Effect of Losartan on the stability of atheromatous plaques in rabbits[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(1): 64-67.

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