罗格列酮联合阿托伐他汀对单核细胞分泌肿瘤坏死因子α的影响

Effects of atorvastain and rosiglitazone on tumor necrosis factor-alpha synthesis

目的研究罗格列酮联合阿托伐他汀干预对无糖尿病的急性冠脉综合征(ACS)患者外周血单核细胞分泌肿瘤坏死因子α(TNF-α)的影响。方法分离无糖尿病的ACS患者外周血单核细胞,设置对照组(等容积的二甲基亚砜)、阿托伐他汀(1μmol/L)组、罗格列酮(1μmol/L)组及二者联合组(阿托伐他汀1μmol/L加罗格列酮1μmol/L组)4个组,分别与所分离的外周血单核细胞共同孵育24 h后,用夹心酶联免疫吸附测定法检测细胞培养上清液TNF-α,用逆转录聚合酶链反应(RT-PCR)测定TNF-αmRNA的表达。结果与对照组相比较,阿托伐他汀组、罗格列酮组及联合组对无糖尿病ACS患者外周血单核细胞分泌TNF-α[分别为(229±24)ng/L、(236±28)ng/L、(159±29)ng/Lvs(306±40)ng/L,均P<0.05]及TNF-αmRNA的相对半定量吸光值(A)比值(分别为0.35±0.12,0.39±0.11,0.26±0.06vs0.78±0.14,均P<0.05)均降低,且罗格列酮联合阿托伐他汀组比阿托伐他汀组、罗格列酮组降低更显著(均P<0.05)。结论阿托伐他汀和罗格列酮都可通过降低无糖尿病的ACS患者外周血单核细胞产生分泌TNF-α,发挥阿托伐他汀和罗格列酮的抗炎作用,且二者联合干预具有协同作用,防治效果更佳。

AIM To investigate the effects of atorvastatin and rosiglitazone on the synthesis of tumor necrosis factor-alpha in peripheral blood monocytes from patients with acute coronary syndrome without diabetes mellitus. METHODS Monocytes were isolated from patients with acute coronary syndrome without diabetes mellitus and cultured with dimethyl sulphoxide （as the control）, atorvastatin （1 μmol/L）, and rosiglitazone （ 1 μmol/L）, or atorvastain （ 1 μmol/L） plus rosiglitazone （ 1 μmol/L） for up to 24 hours. Tumor necrosis factor-alpha antigens in supernatant were measured by enzyme-linked immunosorbent assay and their mRNA levels were assessed by reverse-transcriptase polymerase chain reaction. RESULTS Compared with the control, atorvastatin （1 μmoL/L）, and rosiglitazone （1μmol/L）, or atorvastain （1μmol/L） plus rosiglitazone （1μmol/L） decreased the levels of tumor necrosis factor-alpha protein [ （229 ±24） rig/L, （236 ±28） ng/L, （ 159 ±29） rig/L, vs （306 ±40） ng/L, respectively, all P 〈 0. 05], and their mRNA （0. 35 ±0. 12, 0. 39 ±0. 11, 0.26 ±0. 06 vs O. 78 ±0. 14, respectively, all P 〈0. 05 ） in peripheral blood monocytes from patients with acute coronary syndrome without diabetes mellitus. Furthermore, Compared with the groups of atorvastatin （ 1 μmol/L） or rosiglitazone （ 1 μmol/L）,the groups of atorvastain plus rosiglitazone resulted in more significant reduction （P 〈 0. 05）. CONCLUSION Both atorvastatin and roiglitazone, assuage inflammation through reducing tumor necrosis factor-alpha in peripheral blood monocytes from patients with acute coronary syndrome. Synergistic administration of ator- vastatin and roiglitazone exerts better preventive and therapeutic effects on acute coronary syndrome.