ox-LDL刺激对冠心病患者单核细胞ATP结合盒转运体A1反应性的影响

Effect of ox-LDL on the expression of ATP-binding cassette transporter A1 in monocyte of patients with coronary heart disease

目的研究在氧化型低密度脂蛋白(ox-LDL)刺激下冠心病患者单核细胞三磷酸腺苷结合盒转运体A1(ABCA1)的表达水平及ABCA1在动脉粥样硬化(AS)中的作用机制。方法分别取冠心病患者(42例)及正常对照者(40例)新鲜血液中的单核细胞,利用密度(1.077)梯度离心法分离,PE荧光标记ABCA1,采用流式细胞仪检测其在单核细胞中的表达量。ox-LDL(30mg/L)刺激单核细胞24h后,观察两组ABCA1表达量的变化情况,分析ABCA1表达量与血脂的相关性。结果冠心病组高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A1(apoA1)表达量分别为1.15±1.40,1.19±0.17,与正常对照组(分别为1.36±0.40,1.34±0.22)相比明显降低,差异有统计学意义(P<0.05)。ox-LDL刺激后两组ABCA1表达量均增加,冠心病组单核细胞ABCA1表达量与刺激后表达量增加幅度(ΔABCA1)(分别为9.80±4.62,4.36±2.34)均较正常对照组(分别为29.35±5.17,7.43±1.51)低,差异有统计学意义(P<0.05)。ABCA1表达量与血脂无明显相关性(P>0.05)。结论冠心病患者体内高浓度ox-LDL对ABCA1表达有抑制作用,ABCA1的损伤和异常血脂谱均使患者逆胆固醇转运(RCT)降低,在AS及冠心病的发生、发展中起着重要作用。

Objective To investigate the expression level of monocytes ATP-binding cassette transporter A1（ABCA1） stimulated by oxidized low-density lipoprotein （ox-LDL） in patients with coronary heart disease （CHD） for exploring the mechanism of ABCA1 in the pathogenesis of atherosclerosis （AS）. Methods Human monocytes of patients in CHD group （n=42） and normal control group （n=40） were isolated by density gradient centrifugation with separating medium （1.077）. ABCA1 was labeled by immune reaction PE fluorescence, then the expression of ABCA1 before and after being incubated with the ox-LDL （30mg/L） for 24 hours was investigated by flow cytometer, and the changes in ABCA1 expression were observed. The differences between the two groups and the correlation between ABCA1 expression and blood lipids were analyzed. Results The high-density lipoprotein cholesterol （HDL-C） and apolipoprotein A1 （apoA1） levels in CHD group （1.15±1.40 and 1.19±0.17, respectively） were significantly lower than that in control group （1.36±0.40 and 1.34±0.22, respectively, P〈0.05）. ABCA1 expression stimulated by ox-LDL was elevated in the both groups. After stimulation of ox-LDL, ABCA1 expression in mononuclear cells and the increase rate of ABCA1 expression were elevated in both groups, but they were lower in CHD group （9.80±4.62 and 4.36±2.34, respectively） significantly compared with that in control group （29.35±5.17 and 7.43±1.51, respectively, P〈0.05）. There was no significant correlation between ABCA1 expression and blood lipid level （P〉0.05）. Conclusions ABCA1 expression in the patients with CHD may be inhibited by high concentration of ox-LDL. The lowered expression of ABCA1 and the abnormal lipids spectrum may decrease the reverse cholesterol transport （RCT）, and contribute to the development of AS and CHD.