摘要
目的探讨他汀类降脂药潜在的降脂外机制。方法人单核细胞来源的巨噬细胞与50 mg/L的氧化低密度脂蛋白(oxLDL)共培养10 d,不加入阿托伐他汀作为空白对照组;其他各组分别加入不同浓度的阿托伐他汀(0.01-0.5μmol/L)作为干预组。ELISA法测定基质金属蛋白酶-9(MMP-9)含量,酶谱学分析MMP-9活性;ELISA法测定组织因子(TF)表达,一期凝固法测定TF的促凝活性。结果阿托伐他汀可剂量依赖性抑制单核-巨噬细胞的增殖,加入100μmol/L羟甲戊酸后这种抑制作用消失;0.1μmol/L和0.5μmol/L的阿托伐他汀可显著抑制单核-巨噬细胞MMP-9的表达和活性,以及抑制TF抗原的表达和促凝活性。结论阿托伐他汀可抑制单核-巨噬细胞的增殖,亦可抑制单核-巨噬细胞引起的胶原降解活性和促凝活性。
Objective To investigate the effect of atorvastatin-a HMG-CoA reductase inhibitor on the expression and activity of matrix metalloproteinase-9 （MMP-9） and tissue factor （TF） on human monocytes induced by Oxidized LDL （oxLDL）. Methods Human monocytes-derived macrophages were incubated with oxLDL in the presence or absence of different concentration atorvastatin. At the end of incubation, MMP-9 expression and its activity was assessed by ELISA and zymography analysis respectively. TF expression and its procoagulant activity was assessed by ELISA and a clotting assay respectively. Results The results showed that atorvastatin inhibited human monocytes-derived macrophages proliferation which can be eliminated by adding 100 μmol/L mevalonate. 0. 1 μmol/L and 0. 5 μmol/L atorvastatin can inhibit MMP-9 expression （1.32 ±0. 06 vs 2. 57 ±0. 06 μg/L,P 〈0. 05;1.25 ±0. 04 vs 2. 57 ± 0. 06 μg/L, P 〈 0. 01, respectively）and its activity of human monocytes-derived macrophages significantly, and inhibit TF expression （ 3.34 ± 0. 66 vs 5.78 ± 0. 86 μg/L, P 〈 0. 05 ; 2. 20 ± 0. 60 vs 5.78 ± 0. 86 μg/L, P 〈0. 01 ,respectively） and its procoagulant activity in a concentration-dependant manner. Conclusion Atorvastatin inhibit the proliferation of human monocytes-derived macrophages, and also inhibit MMP-9 and TF expressions and their activities induced by oxLDL, which can lead to collagen degradation and blood clotting.
出处
《基础医学与临床》
CSCD
北大核心
2007年第2期178-182,共5页
Basic and Clinical Medicine
