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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2010年第1期

页码:

12-15,19

栏目:

基础研究

出版日期:

2010-01-04

文章信息/Info

Title:

Effects of losartan on atherosclerotic plaques: stability and expression of MMP-1 and its inhibitor in ApoE gene-deficient mice

作者:

何继强¹; 刘晓惠¹; 王绿娅²; 秦彦文²; 杜兰萍²; 方薇³; 王伟³¹; 武迎³

首都医科大学附属北京安贞医院、北京市心肺血管疾病研究所: 1.心内科,2.动脉粥样硬化研究室,3.病理科,北京100029

Author(s):

HE Ji-qiang¹;  LIU Xiao-hui¹;  WANG Lu-ya²;  QIAN Yan-wen²;  DU Lan-ping²;  FANG Wei³;  WANG Wei³;  WU Ying³

1.Department of Cardiology, 2.Institution of Atherosclerotic Diseases, 3.Department of Pathology, Beijing Anzhen Hospital, Capital Medical University and Beijing Institution of Heart Lung and Blood Vessel Disease, Beijing 100029, China

关键词:

氯沙坦; 基因缺陷小鼠; 斑块稳定; 基质金属蛋白酶-1; 基质金属蛋白酶组织抑制物-1

Keywords:

losartan;  gene-deficient mice;  atherosclerosis;  stabilizing plaque;  matrx metalloproteinase 1;  tissue inhibitor of MMP-1

分类号:

R543.5

DOI:

-

文献标识码:

A

摘要:

目的: 探讨氯沙坦(LST)对载脂蛋白E基因缺陷(ApoE-/-)小鼠主动脉粥样斑块稳定性和基质金属蛋白酶-1（MMP-1）及MMP-1组织抑制物(TIMP-1)蛋白表达影响及可能机制。方法: 将27只8周龄雄性ApoE-/-小鼠随机等分3组，即对照组、低剂量LST ［5 mg/(kg·d)］组及高剂量LST［25 mg/(kg·d)］组。给药16周后处死动物，以常规生化法测定血脂的水平。将主动脉根部连续石蜡切片、HE染色后，观察小鼠主动脉粥样斑块的形成。用免疫组化染色法检测观察粥样斑块中MMP-1和TIMP-1蛋白表达的水平。结果: 3组血脂的水平差异无统计学意义。LST干预后动脉粥样斑块纤维帽厚,脂质核心小，斑块趋于稳定。LST组主动脉斑块中MMP-1蛋白的表达、TIMP-1的比值均显著低于对照组（P<0.01），且高剂量LST较低剂量LST的作用更明显（P<0.01）。结论: LST可通过降低斑块中MMP-1的表达，调节MMP-1/TIMP-1之间的平衡，对粥样斑块具有稳定作用，且呈剂量依赖性，独立于其调节血脂代谢。

Abstract:

AIM: To explore the effects of losartan (LST) on the expressions of matrx metalloproteinase 1 (MMP-1) and tissue inhibitor of MMP-1 (TIMP-1) in aortic atherosclerotic plaques of ApoE gene-deficient (ApoE-/-) mice and to discuss the possible mechanism of LST stabilizing atherosclerotic plaques. METHODS: Twenty seven male 8-week-old ApoE-/- mice were randomly divided into three equal groups: control group, low-dose LST ［5mg/(kg·d)］ group and high-dose LST ［25mg/(kg·d)］ group. The period of administration was 16 weeks. Serum lipid was measured by routine biochemical methods. Consecutive paraffin slices were histochemically colorated to observe the pathological changes of the atherosclerosis (As). The expressions of MMP-1 and TIMP-1 in atherosclerotic plaques were detected by immunological histochemical staining. RESULTS: No significant difference was observed in serum lipids among the three groups. Atheromatous plaques of the two treatment groups contained some thick fibrous caps and little lipid cores, characteristic of stable plaques. The expression of MMP-1 protein and the ratio of MMP-1/TIMP-1 of LST treatment groups were significantly lower than those of control group (P<0.01). Significant differences were also observed between treatment groups (P<0.01). CONCLUSION: With no effect on serum lipids, LST stabilizes plaques through decreasing the expression of MMP-1 protein and modulating the balance of MMP-1/TIMP-1. The impact of stabilizing plaques is concentration dependent.

参考文献/References

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备注/Memo

备注/Memo:

收稿日期：2009-1-15.通讯作者：刘晓惠，主任医师，主要从事冠心病和心脏电生理诊治研究Email：liuxiaohui8838@163.com 作者简介：何继强，主治医师，博士生Email: hejqiang@sina.com

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更新日期/Last Update: 2010-01-05