普萘洛尔对肾上腺素促大鼠动脉粥样硬化斑块进展的保护作用及其机制的研究  

Investigation of the mechanisms of protective effect of propranolol on the progression of atherosclerotic plaque in rats caused by epinephrine

作　　者：周敬群[1] 周军[1,2] 董勇[1] 曾秋棠[3] 杨维华[1] 

机构地区：[1]三峡大学仁和医院心内科,湖北宜昌443001 [2]枝江市人民医院心内科 [3]华中科技大学附属协和医院心内科

出　　处：《临床心血管病杂志》2011年第10期787-790,共4页Journal of Clinical Cardiology

基　　金：湖北省教育厅自然科学研究项目(No:D20091308);湖北省科技厅自然科学基金计划项目(No:2008CDZ093)

摘　　要：目的:探讨普萘洛尔对肾上腺素促大鼠动脉粥样硬化斑块进展的预防作用及其机制。方法:50只Wistar雄性大鼠经高脂喂养17周,制成动脉粥样硬化模型。随机分为对照组、肾上腺素组、普萘洛尔小剂量组、普萘洛尔中剂量组、普萘洛尔大剂量组,每组10只。所有大鼠在继续高脂喂养基础上,对照组皮下注射生理盐水0.5ml/d;肾上腺素组予肾上腺素0.5mg.kg-1.d-1皮下注射;普萘洛尔小、中、大剂量组分别予普萘洛尔2.5mg.kg-1.d-1、5mg.kg-1.d-1、7.5mg.kg-1.d-1灌胃,0.5h后皮下注射肾上腺素0.5mg.kg-1.d-1。分组处理1周,处死全部大鼠,取主动脉粥样斑块用免疫组织化学方法检测巨噬细胞(CD68)浸润及MMP-9表达。结果:肾上腺素组,CD68阳性细胞浸润及MMP-9的表达显著高于对照组;普萘洛尔小、中、大剂量组,CD68阳性细胞浸润程度及MMP-9的表达较肾上腺素组显著减少,且减少程度与普萘洛尔剂量呈正相关。结论:普萘洛尔可以减轻肾上腺素刺激后大鼠动脉粥样硬化斑块内巨噬细胞的浸润及其MMP-9表达,有延缓肾上腺素促大鼠动脉粥样硬化斑块进展的作用。Objective：To investigate the mechanisms of protective effect of propranolol on the progression of atherosclerotic plaque,and to study the changes of expression of CD68 and matrix metalloproteinase-9（MMP-9） in rats caused by epinephrine.Methods：50 male Wistar rats were fed with high cholesterol diet for 17 weeks to establish atherosclerotic model.Then,they were randomly divided into five groups： control group,epinephrine group,propranolol group A,propranolol group B and propranolol group C（10 rats each group）.All groups were continuously fed with high cholesterol diet.At the same time,control group rats were treated with 0.9% sodium chloride 0.5 ml/d,ih;epinephrine group rats were treated with epinephrine 0.5 mg/kg·d,ih;propranolol groups were pretreated with propranolol（group A 2.5 mg/kg·d;group B 5 mg/kg·d;group C 7.5 mg/kg·d） before 30 minutes treatment with epinephrine.After one week,the expressions of CD68 and MMP-9 in the artery atherosclerotic plaque were examined by immunohistochemistry.Results：Compared with control group,the expressions of CD68 and MMP-9 in epinephrine group were significantly increased（P0.05）.Compared with epinephrine group,propranolol groups showed that the expressions of CD68 and MMP-9 in atherosclerotic plaque decreased significantly（P0.05）.Among propranolol groups,with the increase of the propranolol dose,the positive expression of CD68 and MMP-9 were decreased,but no significant difference were observed.Conclusion：Propranolol can delay the progression of atherosclerotic plaque which may due to its effect to attenuate the macrophage infiltration and MMP-9 expression induced by epinephrine.

关 键 词：动脉粥样硬化 普萘洛尔 斑块稳定性 

分 类 号：R543.1[医药卫生—心血管疾病]