【摘要】 目的研究西布曲明对高表达hERG钾通道的HEK293细胞hERG电流的影响。方法构建高表达hERG钾通道的HEK293细胞系,采用全细胞膜片钳技术观察西布曲明对hERG电流的影响。结果西布曲明3、10、30、100μmol/L对电流Iherg-tail的抑制率分别为(8.82±2.32)%、(26.7±5.78)%、(44.93±4.60)%、(85.22±3.37)%,IC50为32.66μmol/L(n=8);西布曲明在30～100μmol/L浓度范围内,在膜电位分别为-10mV～+60mV(step)和0mV～+60mV(tail)时,Ⅰ-Ⅴ曲线显著下移(n=8)。结论西布曲明对hERG电流有显著的浓度依赖性抑制作用,这可能是其导致QT间期延长的主要作用机制。更多还原

【Abstract】 Objective To study the effects of sibutramine on the human-ether-a-go-go-related gene (hERG) current in HEK293 cell line that overexpresses hERG potassium channels. Methods HEK293 cell line that overexpresses hERG potassium channels was constructed. Whole cell patch clamp techniques were employed to investigate the effects of sibutratime on Iherg in the cell line. Results Sibutramine reduced hERG current in a concentration-dependent manner:the inhibition rate was (8.82±2.32)%,(26.7±5.78)%,(44.93±4.60)% and (85.22±3.37)% at the dose of 3,10,30 and 100 μmol/L. IC50 value was 32.66 μmol/L (n=8). Ⅰ-Ⅴ relationship was inhibited by sibutramine (3,10,30 and 100 μmol/L) at membrane potentials from -10 mV to +60 mV (step) and from 0 mV to +60 mV (tail) (n=8). Conclusion Sibutramine significantly inhibited Iherg in HEK293 cell line that overexpresses hERG potassium channels in a concentration-dependent manner,which may be a major mechanism of causing QT interval prolongation.更多还原