白藜芦醇的衍生物白皮杉醇可适度减缓心肌细胞钠电流（I(Na)）失活，并对缺血再灌注大鼠心脏发挥抗心律失常作用。
Piceatannol, a derivative of resveratrol, moderately slows I(Na) inactivation and exerts antiarrhythmic action in ischaemia-reperfused rat hearts.
作者信息
Chen Wen-Pin, Hung Li-Man, Hsueh Chia-Hsiang, Lai Ling-Ping, Su Ming-Jai
机构信息
Institute of Pharmacology, National Taiwan University Medical College, Taipei 100, Taiwan.
出版信息
Br J Pharmacol. 2009 Jun;157(3):381-91. doi: 10.1111/j.1476-5381.2008.00106.x. Epub 2009 Apr 3.
BACKGROUND AND PURPOSE
Piceatannol is more potent than resveratrol in free radical scavenging in association with antiarrhythmic and cardioprotective activities in ischaemic-reperfused rat hearts. The present study aimed to investigate the antiarrhythmic efficacy and the underlying ionic mechanisms of piceatannol in rat hearts.
EXPERIMENTAL APPROACH
Action potentials and membrane currents were recorded by the whole-cell patch clamp techniques. Fluo-3 fluorimetry was used to measure cellular Ca2+ transients. Antiarrhythmic activity was examined from isolated Langendorff-perfused rat hearts.
KEY RESULTS
In rat ventricular cells, piceatannol (3-30 micromol.L(-1)) prolonged the action potential durations (APDs) and decreased the maximal rate of upstroke (V(max)) without altering Ca2+ transients. Piceatannol decreased peak I(Na) and slowed I(Na) inactivation, rather than induced a persistent non-inactivating current, which could be reverted by lidocaine. Resveratrol (100 micromol.L(-1)) decreased peak I(Na) without slowing I(Na) inactivation. The inhibition of peak I(Na) or V(max) was associated with a negative shift of the voltage-dependent steady-state I(Na) inactivation curve without altering the activation threshold. At the concentrations more than 30 micromol.L(-1), piceatannol could inhibit I(Ca,L), I(to), I(Kr), Ca2+ transients and Na+-Ca2+ exchange except I(K1). Piceatannol (1-10 micromol.L(-1)) exerted antiarrhythmic activity in isolated rat hearts subjected to ischaemia-reperfusion injury.
CONCLUSIONS AND IMPLICATIONS
The additional hydroxyl group on resveratrol makes piceatannol possessing more potent in I(Na) inhibition and uniquely slowing I(Na) inactivation, which may contribute to its antiarrhythmic actions at low concentrations less than 10 micromol.L(-1).
背景与目的
在缺血再灌注的大鼠心脏中，白藜芦醇在清除自由基方面比白藜芦醇更有效，且具有抗心律失常和心脏保护活性。本研究旨在探讨白藜芦醇在大鼠心脏中的抗心律失常疗效及其潜在的离子机制。
实验方法
采用全细胞膜片钳技术记录动作电位和膜电流。用Fluo-3荧光测定法测量细胞Ca2+瞬变。从离体Langendorff灌注大鼠心脏检测抗心律失常活性。
关键结果
在大鼠心室细胞中，白藜芦醇（3 - 30 μmol·L-1）延长动作电位时程（APD）并降低最大上升速率（V(max)），而不改变Ca2+瞬变。白藜芦醇降低峰值I(Na)并减慢I(Na)失活，而非诱导持续的非失活电流，这可被利多卡因逆转。白藜芦醇（100 μmol·L-1）降低峰值I(Na)但不减缓I(Na)失活。峰值I(Na)或V(max)的抑制与电压依赖性稳态I(Na)失活曲线的负向移位相关，而不改变激活阈值。在浓度超过30 μmol·L-1时，白藜芦醇可抑制I(Ca,L)、I(to)、I(Kr)、Ca2+瞬变和Na+-Ca2+交换，但不包括I(K1)。白藜芦醇（1 - 10 μmol·L-1）在遭受缺血再灌注损伤的离体大鼠心脏中发挥抗心律失常活性。
结论与启示
白藜芦醇上额外的羟基使白藜芦醇在抑制I(Na)方面更有效，并独特地减缓I(Na)失活，这可能有助于其在浓度低于10 μmol·L-1时的抗心律失常作用。
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