囊性纤维化跨膜调节因子氯离子通道在人肺泡上皮细胞损伤中的保护作用  

The protective effects of cystic fibrosis transmembrane conductance regulator chloride channel on injured human alveolar epithelial cells

作　　者：张丙芳[1] 黄颖[1] 李勇[1] 郭艳艳[2] 张荣怀[1] 招明高[2] 王晓明[1] 

机构地区：[1]第四军医大学西京医院老年病科,西安710033 [2]第四军医大学西京医院药学系药理学教研室,西安710033

出　　处：《解放军医学杂志》2009年第11期1321-1325,共5页Medical Journal of Chinese People's Liberation Army

基　　金：陕西省社会发展科技攻关项目(2009K13-01)

摘　　要：目的探讨人肺泡上皮细胞囊性纤维化跨膜通道调节因子(CFTR)氯离子(Cl-)通道对肺泡上皮细胞损伤的保护作用。方法采用全细胞膜片钳法,在0mV钳制电压下,对正常A549细胞或H2O2处理(氧化损伤)的A549细胞分别按照不同方式给予4-氯苯[F]异喹啉(CBIQ)、二苯胺-2-羧酸(DPC)及钙通道阻断剂尼卡地平,观察细胞从-90mV至50mV经步阶电压(20mV)刺激后CFTRCl-电流随时间变化的曲线,并绘制电流-电压(I-V)曲线。结果正常及H2O2损伤后的细胞中均记录到典型的CFTRCl-电流,均可被相对特异性的CFTRCl-通道阻断剂DPC抑制。H2O2损伤细胞的CFTRCl-电流较正常细胞明显减小。CBIQ对H2O2损伤细胞的CFTRCl-电流以及被DPC+尼卡地平阻断后的正常细胞中的CFTRCl-电流均有激动作用。结论氧化应激可导致CFTRCl-通道功能异常,CBIQ可以抑制这种作用。CFTRCl-通道激活剂CBIQ可能通过调节CFTRCl-通道和Ca2+通道发挥保护受损细胞的作用。Objective To investigate the protective effects of cystic fibrosis transmembrane conductance regulator （CFTR） chloridion （Cl-） channels on injured human alveolar epithelial cells. Methods The whole-cell patch-clamp recordings were applied. Under the holding potential of 0mV,4-Chloro-benzo[F]isoquinoline （CBIQ）,diphenylamine-2-carboxylic acid （DPC,a specific inhibitor of CFTR Cl-channel） and calcium channel inhibitor nicadipine were given to normal human alveolar epithelial A549 cells or oxidization injured A549 cells （treated with H2O2） in different ways. The time curves of CFTR chloridion currents in human alveolar epithelial cells were recorded at a holding potential of 0mV,a testing potential from -90mV to 50mV,a step potential of 20mV by the whole-cell patch clamp technique,and I-V curves were plotted. Results The CFTR Cl-currents were recorded in both normal cells and the oxidation injured cells,and it was found that such currents could be inhibited by DPC. The currents recorded on H2O2 injured cells were much lower than that on normal cells. CBIQ showed an activating effect on the CFTR Cl-currents of H2O2 injured cells and of normal cells previously inhibited by DPC ＋ nicadipine. Conclusions Oxidative stress may lead to abnormality of CFTR Cl-channels which degraded Cl-secretion in the alveolar epithelial cells,and CBIQ may inhibit the effects. CBIQ,the CFTR Cl-channel activator,may play a protective effect on human alveolar epithelial cells through adjustment of CFTR Cl-channels and Ca2＋ channels.

关 键 词：囊性纤维化跨膜传导调节因子 氯化物通道 急性肺损伤 氧化性应激 

分 类 号：R563.9[医药卫生—呼吸系统] R318.1[医药卫生—内科学]