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注射用丹参多酚酸盐对豚鼠心脏电生理和hERG电流的影响

罗卓卡,陈 龙,霍丹,张明珠,何丽霞,王阿芳   

  1. 苏州大学附属常州肿瘤医院;南京中医药大学,南京中医药大学,苏州大学附属常州肿瘤医院,苏州大学附属常州肿瘤医院,苏州大学附属常州肿瘤医院,苏州大学附属常州肿瘤医院
  • 收稿日期:2018-04-16 修回日期:2018-04-16 出版日期:2018-06-25 发布日期:2018-06-25
  • 基金资助:
    江苏省药学会—奥赛康医院药学科研项目(201411)。江苏现代医院管理研究基金(JSY-3-2017-033)

Effect of Salvianolate for Injection on Electrophysiological Action of Guinea Pig Hearts and hERG Currents

Luo Zhuoka,,,, and   

  1. The Changzhou Tumor Affiliated Hospital of Soochow University;China;School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,;China,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,The Changzhou Tumor Affiliated Hospital of Sooch
  • Received:2018-04-16 Revised:2018-04-16 Online:2018-06-25 Published:2018-06-25

摘要: 目的:研究注射用丹参多酚酸盐(ZDDY)对豚鼠心脏电生理的影响,并对注射用丹参多酚酸盐的心脏安全性做出评价。方法:采用常规豚鼠在体心电图技术,改进的Langendoff灌流系统,常规细胞内动作电位记录法和膜片钳全细胞记录方法,观察药物对整体和离体心电图,动作电位时程(Action Potential Durations,APDs)以及人ether-a-go-go-related gene(hERG)通道电流的影响。结果: ZDDY 460.0 mg?kg-1使在体心电图PR间期从(61.0±2.8)ms延长到(70.9±0.9)ms;QRS间期从(15.3±1.8)ms延长到(17.0±2.1)ms,比较差异均具有统计学意义。ZDDY 0.51 mg?mL-1使离体心脏的心率(Heart Rate,HR)从(177.3±11.1)bpm减慢到(152.0±1.7)bpm,差异具有统计学意义。ZDDY 各浓度组对APDs和动作电位振幅(Amplitudes of Action Potential,APA)无影响。ZDDY 抑制50%hERG电流的浓度(Half Maximal Inhibitory Concentration,IC50)为(10.8±0.6)mg?mL-1。结论: 注射用丹参多酚酸盐在临床剂量下对豚鼠在体心脏作用安全;高剂量下对离体豚鼠心脏有减慢心率作用。

Abstract: Objective: To study the preclinical cardiac electrophysiology physiological characteristics of Salvianolate for injection(ZDDY) and the cardiac safety of ZDDY was evaluated. Methods:In vivo, in vitro ECG and intracellular action potential recording techniques were used to analyze the P-R,QRS,QTs and heart rate(HR). Recording of hERG current from HEK cell line cloned with hERG cDNA. Results:PR interval of guinea pigs in vivo was prolonged that ZDDY was given by 460.0 mg?kg-1, prolonged from (61.0±2.8) ms to (70.9±0.9 ms) (P<0.05, n=12), while QRS duration was significantl prolonged from (15.3±1.8) ms to (17.0±2.1) ms (P<0.05, n=12) . ECG of guinea pigs in vitro showed that after perfusion of 0.51 mg?mL -1ZDDY, heart rate (HR) of guinea pigs in vitro was significantly slowed down from (177.3±11.1) bpm to (152.0±1.7) bpm (P<0.05, n=6), and heart rate of washout group was slightly restored.There was non effect of various concentrations of ZDDY on the action potential APD50, APD90 and action potential amplitude (APA). ZDDY inhibited the hERG currents with the IC50 of (10.8±0.6)mg?mL -1.Conclusion: The Clinical dose of ZDDY was found safe for heart of in vivo guinea pig, and no cardiac adverse events was observed. But ZDDY might slow the in vitro heart rate at high-doses.