氧化低密度脂蛋白对人单核细胞组织因子和基质金属蛋白酶-9活性的影响以及阿托伐他汀的干预作用  

Interventional effect of atorvastatin on matrix metalloproteinase-9 and tissue factor induced by oxidized LDL in human monocytes

作　　者：童国新[1] 陈鹏[2] 王宁夫[1] 张邢炜[1] 徐坚[1] 朱永良[2] 

机构地区：[1]杭州市第一人民医院心内科,杭州310006 [2]浙江大学医学院附属第二医院心内科

出　　处：《临床心血管病杂志》2006年第11期677-680,共4页Journal of Clinical Cardiology

摘　　要：目的：探讨他汀类降脂药阿托伐他汀潜在的降脂外机制。方法：人单核细胞来源的巨噬细胞，加入50mg／L氧化低密度脂蛋白（oxLDL）共培养10d，加或不加入不同浓度的阿托伐他汀（浓度范围0．01～0．5μmol／L）；酶谱学分析基质金属蛋白酶-9（MMP-9）的活性；一期凝固法测定组织因子（TF）的促凝活性。结果：阿托伐他汀可抑制单核-巨噬细胞的增殖，呈现一定的剂量依赖关系（P〈0．05），加入100μmol／L羟甲戊酸后，这种抑制作用消失；0．1μmol／L的阿托伐他汀可显著抑制单核-巨噬细胞表达MMP-9的活性；阿托伐他汀可呈剂量依赖性抑制TF的促凝活性（P〈O．05）。结论：阿托伐他汀不仅可抑制单核一巨噬细胞的增殖，而且可抑制单核巨噬细胞活化下表达的MMP-9的活性以及TF的促凝活性。Objective：To investigate the effect of atorvastatin-a HMG-CoA reductase inhibitor on Matrix Metalloproteinase-9 （MMP-9） and tissue factor（TF） activity on human monocytes induced by oxidized LDL （oxLDL）. Method： Human monocytes-derived macrophages were incubated with oxLDL in presence or absence of different concentrations of atorrastatin （0.01 ～0.05 μmol/L） for 10 days. At the end of incubation, MMP-9 activity was assessed by zymography analysis,and TF procoagulant activity was assessed by a one-stage clotting assay. Result： The results showed that atorvastatin inhibited human monocytes-derived macrophages proliferation in a dose-dependent manner （ P 〈0.05）, which could be eliminated by adding 100 μmol/L mevalonate; 0.1 μmol/L atorvas- tatin could inhibit MMP-9 activity on human monocytes-derived macrophages significantly, and inhibit TF procoagulant activity in a dose-dependent manner （ P 〈0.05）. Conclusion： Atorvastatin can not only inhibit human monocytes-derived macrophages proliferation,but also inhibit MMP-9 activity and TF procoagulant activity on human monocytes-derived macrophages.

关 键 词：阿托伐他汀 氧化低密度脂蛋白 基质金属蛋白酶-9 组织因子 

分 类 号：R972[医药卫生—药品]