摘要
目前的心肌细胞电生理实验已证实，在影响动作电位时程（Action Potential Duration，APD）长短以及动作电位形态改变的电流中，瞬时外向性钾电流（Transient Outward Potassium Current，I10）是在其变化中担任重要角色的钾电流之一。炙甘草汤是医圣张仲景《伤寒论》中治疗脉结代古方，临床上广泛用于治疗各种心律失常。基础实验研究发现炙甘草汤具有抑制由药物诱发的心肌细胞异常自律性和兴奋性以及各种触发性心律失常，延长由药物引起心肌细胞APD的缩短而引起的各种心律失常。以往研究炙甘草汤药理机制都是通过体外直接加复方制剂的方法。目前多采用血清药理学方法。本文应用全细胞膜片钳技术观察炙甘草汤含药血清对家兔心室肌细胞的影响，从离子通道水平探讨炙甘草汤发挥抗心律失常的药理效应，为进一步研究其作用于心肌相应钾通道的机制提供理论依据。
Objective: To investigate the effect of Serum Containing Zhi Gancao Decoction on transient outward potassium current (I_ to ) and its kinetic influence on isolated ventricular myocytes of rabbits.Method: Seperated ventricular myocytes were enzymatically dissociated from adult rabbits.The drug concentration of Zhi Gancao Decoction contained serum was examined by serologic pharmacological test.Whole-cell patch clamp technique was used to record voltage-dependent I_ to of ventricular myocytes of rabbit.Results: (1)Serum containing Zhi Gancao Decoction (20) significantly decreased I_ to through a voltage-dependent way after a 5 minute action.With command potential of +50mV,the peak current density of I_ to was significantly decreased from (43.3±5.89)pA pF to (7.98±2.78)pA pF(n=6,P<0.01).After washouted for 5 min,I_ to was recovered.(2) It significantly reduced I_ to in an obvious concentration-dependent manner at the range of 5～40 with an IC50 mean value of 12.18.(3) Serum containing Zhi Gancao Decoction (20) significantly shifted I-V curve downward but didn't change the shape of I-V curve.(4) Activation curve of I_ to didn't significantly change before and after administration of Serum containing Zhi Gancao Decoction (20).However,serum containing Zhi Gancao Decoction (20) shifted the inactivation curve leftward,and voltages at 50 Ito inactivation were (-41.4 3.5)mV and (-79.9±2.9)mV(n=8,P<0.05),respectively.(5) After perfusing Serum containing Zhi Gancao Decoction (20),the recovering time of 50 I_ to were(18.2±2.5)ms and(44.1±2.2)ms(n=8,P<0.01),respectively.Conclusion: Serum containing Zhi Gancao Decoction significantly blocked I_ to in rabbit ventricular myocytes.This may be one of ionic channel mechanisms of Serum containing Zhi Gancao Decoction in the treatment of antiarrhythmia in clinical practice.
出处
《微循环学杂志》
2006年第4期19-23,共5页
Chinese Journal of Microcirculation
基金
湖北省自然科学基金项目(2003ABA155)
