工业污染区PM2.5对HEK293细胞表达hERG钾通道和Nav1.5钠通道的影响

Effect of PM2.5 from industrial areas on expression of potassium channel hERG and sodium channel Nav1.5 in HEK293 cells

关键词: PM_2.5  心脏毒性  hERG 钾离子通道  Nav1.5钠离子通道

Keywords: particulate matter 2.5 μm (PM_2.5)  cardiotoxicity  hERG potassium ion channel  Nav1.5 sodium ion channel

摘 要: 目的 研究工业污染区 PM_2.5 对去极化 Nav1.5 钠离子通道和复极化 hERG 钾离子通道的影响。方法 采集工业污染区和非污染城区的空气制备 PM_2.5样本,采用气相色谱质谱联用仪(GC-MS)和电感耦合等离子体质谱(ICPMS)分析其中的多环芳烃类、金属离子和无机盐离子等主要成分,采用 Nav1.5-HEK293 细胞和 hERG-HEK293 细胞分别测试 10、30、100、300、1000μg/ml 浓度时 PM_2.5 的抑制作用。结果 在 10~1000μg/ml 浓度时工业污染区的PM_2.5样本对 hERG 钾离子通道呈浓度依赖性的抑制作用;工业污染区和非污染城区的 PM_2.5对 Nav1.5 钠离子通道均有明显的抑制作用,半数抑制浓度(IC₅₀)分别为 90 和 200μg/ml。结论 PM_2.5对心肌细胞钠、钾离子通道的抑制作用可能是其心脏毒性作用机制之一。

Abstract: Objective Study the effects of PM_2.5 from industrial polluted areas on the depolarization of Nav1.5 sodium ion channel and the repolarization of hERG potassium ion channel.Methods The air samples from polluted industrial areas and non-polluted urban areas to prepare PM_2.5 samples,analyze the main components such as polycyclic aromatic hydrocarbons,metal ions, and inorganic salt ions using gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma mass spectrometry (ICP-MS),test the inhibitory effects of PM_2.5 at concentrations of 10,30,100,300,and 1000μg/ml,using Nav1.5-HEK293 cells and hERG-HEK293 cells,respectively.Results The results showed that at the concentration of PM_2.5 between 10~ 1000μg/ml,the samples from polluted industrial area exhibited concentration dependent inhibitory effect on hERG potassium ion channels;while the PM_2.5 samples both from industrial polluted area and the non-polluted urban area exhibited significant inhibitory effects,with the half-maximal inhibitory concentrations (IC₅₀) of 90 and 200μg/ml,respectively.Conclusion The results suggested that the inhibitory effect of PM_2.5 on sodium and potassium ion channels may be one of its mechanisms of cardiotoxicity.