应用膜片钳技术研究豆腐果苷对hERG钾通道电生理功能的影响

中国临床药理学与治疗学 ›› 2015, Vol. 20 ›› Issue (3): 252-255.

应用膜片钳技术研究豆腐果苷对hERG钾通道电生理功能的影响

贾元威¹, 汪旻晖¹, 谢海棠¹, 沈杰¹, 张晓楠², 司进辉³, 张翠锋⁴

¹皖南医学院弋矶山医院安徽省药物临床评价中心,芜湖 241001,安徽;
²河北尚沃医疗器械有限公司研发部,石家庄 050092,河北;
³河北华建天诚医药有限公司研发部,石家庄 050000,河北;
⁴皖南医学院基础医学院,芜湖 241001,安徽

收稿日期:2014-12-15 修回日期:2015-01-22 发布日期:2015-04-08
通讯作者: 沈杰,男,博士,助理研究员,主要研究方向:药学。Tel: 0553-5738200 E-mail: jie_shen23@aliyun.com;张晓楠,女,研究员,主要研究方向:药学。Tel: 13703353777 E-mail: article2027@sohu.com
作者简介:贾元威,女,博士,助理研究员,主要研究方向:药学。Tel: 0553-5738200 E-mail: 65227734@qq.com
基金资助:
安徽省科技厅自然科学基金项目(1408085MH163);国家自然科学基金项目(81173134);安徽省卫生厅临床医学重点应用技术项目(2010A013);弋矶山医院引进人才科研基金资助项目

Using patch clamp technique to investigate influence of helicid to electrophysiological function of hERG potassium channel

JIA Yuan-wei¹, WANG Min-hui¹, XIE Hai-tang¹, SHEN Jie¹, ZHANG Xiao-nan², SI Jin-hui³, ZHANG Cui-feng⁴

¹Drug Clinical Evaluation Center of Anhui Province, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui,China;
²Hebei SUNVOU Medical Devices Co., Ltd. Shijiazhuang 050092, Hebei,China;
³Hebei Huajian tiancheng Pharmaceutical Co., Ltd, Shijiazhuang 050000, Hebei,China;
⁴Basic medical College, Wannan Medical College, Wuhu 241001, Anhui, China

Received:2014-12-15 Revised:2015-01-22 Published:2015-04-08

摘要/Abstract

摘要： 目的: 探讨豆腐果苷对hERG钾离子电流的影响及潜在心脏毒性。方法: 使用稳定转染hERG基因的CHO细胞,通过全细胞膜片钳技术检测不同浓度豆腐果苷对hERG通道电流活动的作用。结果: 豆腐果苷对hERG钾通道的IC₅₀约为47 μmol/L,比临床常规剂量下人体内峰浓度高1 000倍以上。结论: 临床常用剂量下,豆腐果苷发生与hERG通道抑制作用相关的心脏安全性问题的可能性非常小。

关键词: 豆腐果苷, hERG 钾通道, 全细胞膜片钳技术, 心脏毒性

Abstract: AIM: To investigate the impact of natural medicine helicid on hERG potassium currents and potential cardiac toxicity.METHODS: hERG gene was stably transfected in CHO cells. The whole-cell patch-clamp technique was applied to detect effects on hERG channel current of different concentrations helicid.RESULTS: IC₅₀ of helicid on hERG channels was 47 μmol/L, which was more than 1000 times higher than the peak concentration in human body at clinical dose.CONCLUSION: It is less likely to encounter cardiac safety issues via the hERG channel inhibition of helicid in clinical application.

Key words: helicid, hERG potassium channels, patch-clamp technique, cardiotoxicity

中图分类号:

R965.2

贾元威, 汪旻晖, 谢海棠, 沈杰, 张晓楠, 司进辉, 张翠锋. 应用膜片钳技术研究豆腐果苷对hERG钾通道电生理功能的影响[J]. 中国临床药理学与治疗学, 2015, 20(3): 252-255.

JIA Yuan-wei, WANG Min-hui, XIE Hai-tang, SHEN Jie, ZHANG Xiao-nan, SI Jin-hui, ZHANG Cui-feng. Using patch clamp technique to investigate influence of helicid to electrophysiological function of hERG potassium channel[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(3): 252-255.

参考文献

[1] 刘史佳, 居文政, 谈恒山. 豆腐果苷研究进展[J]. 中国医药导刊, 2008, 6(10): 911-913.
[2] 杨蓉, 肖涵, 戴晓畅. 豆腐果苷抗抑郁作用研究[J]. 中药药理与临床, 2007, 23(6): 22-23.
[3] Jia Y, Xie H, Wang G, et al. Quantitative determination of helicid in rat biosamples by liquid chromatography electrospray ionization mass spectrometry[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2010, 878(9/10): 791-797.
[4] 贾元威, 谢海棠, 王广基, 等.豆腐果苷在大鼠体内代谢的初步研究[J]. 中国药理学通报,2011, 27(1): 144-145.
[5] 贾元威,谢海棠,孙建国, 等. HPLC-ESI-MS方法测定Beagle犬血浆中豆腐果苷浓度[J]. 中国新药杂志, 2009, 18(24):1365-1369.
[6] Laverty H, Benson C, Cartwright E, et al. How can we improve our understanding of cardiovascular safety liabilities to develop safer medicines[J]? Br J Pharmacol,2011, 163(4):675-693.
[7] Kannankeril PJ, Roden DM. Drug-induced long QT and torsade de pointes: recent advances[J]. Curr Opin Cardiol, 2007, 22(1):39-43.
[8] Saiz J, Ferrero JM, Monserrat M, et al. Effects of the antiarrhythmic drug dofetilide on myocardial electrical activity: a computer modelling study[J]. Computers in Cardiology ,2003, 30:291-294.
[9] Xie H, Jia Y, Tan Z, et al. Sensitive and specific LC-MS/MS method for quantitation of helicid in human plasma[J].J Chromatogr B Analyt Technol Biomed Life Sci,2011, 879(30): 3607-3611.
[10]Farkas AS, Nattel S. Minimizing repolarization-related proarrhythmic risk in drug development and clinical practice[J]. Drugs, 2010, 70(5):573-603.
[11]Pugsley MK, Authier S, Towart R, et al. Beyond the safety assessment of drug-mediated changes in the QT interval... what's next[J]? J Pharmacol Toxicol Methods,2009, 60(1):24-27.
[12]Valentin JP, Pollard C, Lainée P, et al. Value of non-clinical cardiac repolarization assays in supporting the discovery and development of safer medicines[J]. Br J Pharmacol,2010, 159(1):25-33.
[13]Konstantopoulou A, Tsikrikas S, Asvestas D, et al. Mechanisms of drug-induced proarrhythmia in clinical practice[J]. World J Cardiol, 2013, 5(6):175-185.
[14]谢海棠, 王果, 范岚, 等. 豆腐果苷对人孕烷X受体介导的CYP3A4和MDR1的转录调节作用[J]. 中国临床药理学与治疗学, 2008, 13(12):1416-1421.