普萘洛尔对大鼠动脉粥样硬化斑块内MMP-9及TIMP-1表达的影响

目的探讨普萘洛尔对大鼠动脉粥样硬化斑块内基质金属蛋白酶-9(MMP-9)及金属蛋白酶组织抑制剂-1(TIMP-1)表达的影响。方法30只Wistar大鼠经高脂、高维生素D、免疫损伤处理17周造成动脉粥样硬化模型,随机分为对照组和普萘洛尔组,每组15只。所有大鼠在继续高脂喂养基础上,普萘洛组予普萘洛尔5mg/(kg.d)灌胃;对照组予生理盐水1ml/d灌胃,一周后处死全部大鼠,取主动脉粥样硬化斑块用免疫组织化学方法检测动脉粥样硬化斑块内巨噬细胞浸润、MMP-9及TIMP-1表达。结果普萘洛尔组巨噬细胞浸润数目及MMP-9的表达较对照组明显减少(P0.01),TIMP-1表达明显增高(P0.05)。结论普萘洛尔减少大鼠动脉粥样硬化斑块处巨噬细胞浸润及MMP-9表达,增加TIMP-1表达,具有稳定动脉粥样硬化斑块作用。

Influences of propranolol on expressions of MMP-9 and TIMP-1 in atherosclerotic plaque in rats

Objective To investigate the mechanism of β-blocker in the stabilization of atherosclerotic plaque through studying the influences of propranolol on expressions of matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） in atherosclerotic plaque in rats.Methods The atherosclerotic model was established in rats by high fat and high vitamin D diet,and immunologic injury for 17 days in 30 Wistar rats.All rats were randomly divided into the control group and propranolol group （each n=15）,and then the propranolol group was given intragastrically propranolol [5 mg/（kg·d） ]and the control group was given intragastrically the normal saline water （1 ml/d） on the base of continued high fat diet.After one week all rats were killed and the atherosclerotic plaque was collected.The macrophage （CD68） infiltration,and expressions of MMP-9 and TIMP-1 in atherosclerotic plaque were detected by using immunohistochemistry assay.Results The number of CD68 infiltration and MMP-9 expression decreased significantly （P0.01）,and TIMP-1 expression increased significantly （P0.05） in the propranolol group compared with those in the control group.Conclusion Propranolol can relieve macrophage infiltration,reduce MMP-9 expression and improve TIMP-1 expression in atherosclerotic plaque to stabilize atherosclerotic plaque.