吉非贝齐对人巨噬细胞Kv1.3和Kir2.1表达的差别调节作用及其对膜电位的影响

目的:探讨人巨噬细胞发育过程中Kv1.3、Kir2.1通道的表达和吉非贝齐的调节作用，观察其对膜电位的影响，为动脉粥样硬化（AS）相关性疾病治疗提供电生理学依据。方法：健康人外周血单核细胞源性巨噬细胞随机分为对照5 d组（C 5d）、对照7.5 d组（C 7.5d）和吉非贝齐组（G），吉非贝齐的终浓度为400 μmol?L^-1；采用Real time RT-PCR及Western blotting技术检测Kv1.3和Kir2.1通道的表达，电压敏感染料膜电位标测技术分析膜电位的变化。结果：与C 5d组比较，C 7.5d组Kv1.3 mRNA/蛋白水平从（1.064±0.275）/（0.227±0.018）升高至（3.067±0.824）/（0.409±0.022）（P<0.05），但Kir2.1 mRNA/蛋白水平却从（1.024±0.166）/（0.204±0.018）降低至（0.399±0.133）/（0.042±0.008）（P<0.05）；与C 7.5d组比较，吉非贝齐组Kv1.3 mRNA/蛋白水平下降至（1.137±0.067）/（0.143±0.023）（P<0.01），而Kir2.1 mRNA/蛋白水平却升高至（1.35±0.087）/（0.202±0.033）（P<0.01）；吉非贝齐显著消弱C 5d和C 7.5d组巨噬细胞表面的荧光强度，使其膜电位从（1.000±0.026）分别下降至（0.833±0.046）和（0.481±0.053）（P<0.05）。结论：吉非贝齐差别调节人单核细胞源性巨噬细胞Kv1.3和Kir2.1通道的表达，并降低巨噬细胞膜电位。

Differential regulation of Kv1.3 and Kir2.1 expression by gemfibrozil in human macrophages and its effects on their membrane potentials

Objective To explore the development change of Kv1.3 and Kir2.1 channels in human macrophages and the effects of gemfibrozil on both channels’ expression and their membrane potentials,which will provide electrophysiologic basis for its treating atherosclerotic diseases.Methods The obtained human monocyte-derived macrophages were randomly divided into 3 groups: control 5 d group(C 5d),control 7.5 d group(C 7.5d) and gemfibrozil group(G).The final concentration of gemfibrozil was 400 μmo·L-1.The effect of gemfibrozil on the expressions of Kv1.3 and Kir2.1 channels was investigated using Real time RT-PCR and Western blotting,and its effect on membrane potentials was analyzed with the optical mapping of the membrane potential with the voltage-sensitive dyes.Results Compared with C 5d group,the expressions of Kv1.3 mRNA/protein in C 7.5d group were raised from(1.064±0.275)/(0.227±0.018) to(3.067±0.824)/(0.409±0.022)(P<0.05),but the expressions of Kir2.1 mRNA/protein were decreased from(1.024±0.166)/(0.204±0.018) to(0.399±0.133)/(0.042±0.008)(P<0.05).Compared with C 7.5d group,the expressions of Kv1.3 mRNA/protein in gemfibrozil group were reduced to(1.137±0.067)/(0.143±0.023)(P<0.01);however,the expressions of Kir2.1 mRNA/protein were elevated to(1.35±0.087)/(0.202±0.033)(P<0.01).Meanwhile,gemfibrozil significantly reduced the surface fluorescence intensity of the macrophages,and the membrane potentials in C 5d and C 7.5d groups were decreased from(1.000±0.026) to(0.833±0.046) and(0.481±0.053),respectively(P<0.05).Conclusion Gemfibrozil differentially regulates the expressions of Kv1.3 and Kir2.1 channels in human monocyte-derived macrophages,and lowered their membrane potentials.