阿托伐他汀对急性冠脉综合征患者外周血单核细胞合成组织因子和TNF-α的影响

Effects of atorvastain on tissue factor and tumor necrosis factor-alpha synthesis in peripheral blood monocytes from patients with acute coronary syndrome

目的:研究阿托伐他汀对急性冠脉综合征患者外周血单核细胞表达TNFα-、组织因子水平及组织因子活性的影响。方法:分离急性冠脉综合征患者外周血单核细胞,分别以不同浓度的阿托伐他汀(0,0.1,1,10μmol/L)干预,共同孵育24 h后,用夹心酶联免疫吸附测定法检测细胞培养上清液TNFα-及细胞膜组织因子水平,用逆转录聚合酶联链反应测定它们mRNA的表达,同时用底物发光法检测组织因子的活性。结果:不同浓度的阿托伐他汀(0,0.1,1,10μmol/L)干预后急性冠脉综合征患者外周血单核细胞合成TNFα-分别为(306±40)、(264±54)、(229±24)、(189±44)ng/L,合成组织因子分别为(5.8±1.3)、(4.6±0.8)、(3.7±0.9)、(2.7±0.5)ng/L及组织因子的活性分别为(16.2±3.2)、(7.7±2.8)、(4.3±0.8)、(3.8±0.8)pmol/L(均P<0.05)。结论:阿托伐他汀呈药物浓度依赖性地减少急性冠脉综合征患者外周血单核细胞合成TNF-α、组织因子及组织因子活性。阿托伐他汀通过抗炎、抗血栓形成而在急性冠脉综合征防治中起重要作用。

AIM： To explore the effects of atorvastatin on the expression of tissue factor and TNF-α, and the tissue factor activity in peripheral blood monocytes from patients with acute coronary syndrome. METHODS： Monocytes were isolated from patients with acute coronary syndrome and cultured with atorvastatin （0, 0.1,1,10 μmol/L） for up to 24 hours. The tissue factor and tumor necrosis factor-alpha antigens in culture medium and cells were measured by enzyme-linked immunosorbent assay. The tissue factor activity was examined by chromogenic substrate assay and the mRNA levels were assessed by reverse-transcriptase polymerase chain reaction. RESULTS： Atorvastatin （0,0.1,1,10 μmol/L） dose-dependently decreased the levels of tissue factor [〈5.8± 1.3）, （4.6±0.8）, （3.7±0.9） and （2.7 ± 0.5） ng/L, respectively] （ P 〈 0.05）, and the activity of tissue factor [（16.2 ± 3.2）, （7.7 ± 2.8）, （4.3±0.8） and （3.8±0.8） μmol/L]（P 〈 0.01 ） in peripheral blood monoeytes from patients with acute coronary syndrome. These alterations were accompanied by a reduction in the levels of TNF-α [ （306±40）, （264 ± 54）,（229 ± 24） and （189 ± 44）ng/L, respectively] （ P 〈 0.05 ）. CONCLUSION： The findings showed that atorvastatin reduced the tissue factor, TNF-α synthesis and tissue factor activity in peripheral blood monocytes from patients with acute coronary syndrome, and thus potentially had the preventive and therapeutic effects on acute coronary syndrome.