南方医科大学学报2012，Vol.32Issue(8)：1067-1073,7.DOI:10.3969/j.issn.1673-4254.2012.08.01
双氯芬酸对人巨噬细胞钾通道Kv1.3、Kir2.1表达的抑制作用及其对膜电位和泡沫细胞形成的影响
Diclofenac inhibits Kvl.3 and Kir2.1 expressions in human macrophages and affects the membrane potential and foam cell formation
摘要
Abstract
Objective To investigate the effect of diclofenac on the expression of Kv1.3 and Kir2.1 channels in human macrophages and the membrane potential and foaming process of the macrophages.Methods The effect of diclofenac on the expression of Kv1.3 and Kir2.1 channels in cultured human monocyte-derived macrophages was investigated using real-time RT-PCR and Western blotting,and its effect on the membrane potential was analyzed with optical mapping of the membrane potential with voltage-sensitive dyes.The ratio of cholesterol ester (CE) in the macrophages following intake of oxidized low-density lipoprotein (OxLDL) was analyzed by an enzymatic fluorometric method.Results The expression of Kv1.3 and Kir2.1 channels in the macrophages were down-regulated by diclofenac (1.5 μmol/L and 15 μmol/L).Compared with those in the control group,Kv1.3 mRNA expression was reduced by over 80％ and 90％ (P＜0.05),and Kir2.1 mRNA by over 20％ and 30％ (P＞0.05),respectively; both their protein expression was reduced by over 10％ and 60％ with a dose- dependent effect (P＜0.05).Diclofenac at the two doses dose-dependently reduced the surface fluorescence intensity of the macrophage,and the membrane potential was decreased by 28％ and 54％,respectively (P＜0.05).Incubation of the macrophages with 30 mg/L OxLDL for 60 h caused an obvious enlargement of the cell volume and deposition of numerous lipid granules in cytoplasm,resulting also in a CE/TC ratio over 50％ (P＜0.05).Diclofenac at 1.5 and 15 μmol/L both significantly decreased the CE/TC ratio to (23.624±3.34)％ and (13.601±2.916)％ (P＜0.05),respectively,but this effect did not show a dose-response relationship (P＞0.05).关键词
离子通道/膜电位/巨噬细胞/双氯酚酸/细胞分化Key words
ionic channels/membrane potential/macrophages/diclofenac/cell differentiation分类
医药卫生引用本文复制引用
雷新军,张葳,林显丰,王东琦,袁祖贻..双氯芬酸对人巨噬细胞钾通道Kv1.3、Kir2.1表达的抑制作用及其对膜电位和泡沫细胞形成的影响[J].南方医科大学学报,2012,32(8):1067-1073,7.基金项目
Supported by National Natural Science Foundation of China (81170276),Natural Science Foundation of Shaanxi Province (2009JM4006),and Xi'an Jiaotong University Medical Innovation Fund (JH0203111).国家自然科学基金(81170276) （81170276）
陕西省自然基金(2009JM4006) （2009JM4006）
西安交通大学医学创新基金(JH0203111) （JH0203111）
