手动膜片钳检测HMS-01对HEK293细胞hERG通道电流的影响  

The effect of HMS-01 on stably expressed hERG channel currents in HEK293 cells detected with the manualpatch clamp method

作　　者：张慧敏 向科发 史小飞 秦臻 刘霞 ZHANG Huimin;XIANG Kefa;SHI Xiaofei;QIN Zhen;LIU Xia(Department of Clinical Pharmacy,School of Pharmacy,Naval Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学药学院临床药学教研室,上海200433

出　　处：《药学实践杂志》2022年第2期132-135,142,共5页Journal of Pharmaceutical Practice

基　　金：国家自然科学基金项目(82073842);上海市2021年度“科技创新行动计划”优秀学术/技术带头人计划项目(21XD1404700)。

摘　　要：目的检测新化合物HMS-01有无心脏毒性,对其进行临床前安全评价研究,为进入临床试验做准备。方法用手动膜片钳检测转染后hERG钾通道稳定表达的HEK293细胞的电流,西沙必利做阳性药,将HMS-01依次稀释成0.3、1、3、10、30μmol/L,依次作用于细胞,记录电流变化,计算抑制率。结果HMS-01在实验设计的最高浓度30μmol/L时,对细胞hERG钾通道的抑制率低于30%,与阳性对照药西沙必利相比,无明显抑制作用。结论新化合物HMS-01对hERG通道无明显抑制作用,不具有心脏毒性。Objective To test the cardiac toxicity of new compound HMS-01 and evaluate the safety profile for clinical trials.Methods Manualpatch clamp method was used to measure human Ether-a-go-go-Related Gene(hERG)potassium channel currents with different concentrations of HMS-01.Cisapride was selected as the positive control drug.HMS-01 was diluted to the concentration of 0.3,1,3,10 and 30μmol/L and applied to the cells.The changes in electrical currents were recorded and the inhibition rate was calculated.Results At the highest concentration of 30μmol/L,the inhibitory rate of HMS-01 on hERG channel was less than 30%.There was no obvious inhibitory effect compared with cisapride.Conclusion Compared with the cisapride,HMS-01 has no obvious inhibitory effect on hERG channel and has no cardiotoxicity.

关 键 词：手动膜片钳 HEK293细胞 HERG通道 

分 类 号：R965[医药卫生—药理学]