化合物TJ0711的抗心律失常作用  

Antiarrhythmic effect of TJ0711

作　　者：张小婧[1] 裘军[1] 李高[1] 

机构地区：[1]华中科技大学同济医学院药学院,湖北武汉430030

出　　处：《药学学报》2014年第3期419-423,共5页Acta Pharmaceutica Sinica

基　　金：国家"重大新药创制"科技重大专项资助项目(2009ZX09103-146;2012ZX09102101-016);湖北省研究与开发计划项目(2008BCB103)

摘　　要：心律失常是心血管疾病患者猝死的主要原因之一，它可以加重原有心脏疾病的进展，并可导致患者突然死亡，严重威胁人类健康。临床和流行病学研究表明，交感神经功能的增强与心律失常的发生密切相关,β受体阻断剂可抑制交感神经的活性，从而发挥抗心律失常的作用。To study the antiarrhythmic effect of the newly developed a/fl-blocker TJ0711, a variety of animal models of arrhythmia were induced by CaCl2, ouabain and ischemia/reperfusion. Glass microelectrode technique was used to observe action potentials of right ventricular papillary muscle of guinea pig. The onset time of arrhythmia induced by CaCl2 was significantly prolonged by TJ0711 at 0.75, 1.5 and 3 mg ·kg^-1 doses. TJ0711 （1.5 and 3 mg ·kg^-1） can significantly shorten the ventricular tachycardia （VT） and ventricular fibrillation （VF） duration, the incidence of VF and mortality were significantly reduced. On ischemia-reperfusion-induced arrhythmic model, TJ0711 （0.25, 0.5, 1 and 2 mg·kg^-1） can significantly reduce the ventricular premature contraction （PVC）, VT, VF incidence, mortality, arrhythmia score with a dose-dependent manner. At the same time, rats serum lactate dehydrogenase （LDH） and creatine kinase （CK） activities decreased significantly by TJ0711 （1 and 2 mg·kg^-1）. Ouabain could cause arrhythmia in guinea pigs, when TJ0711 （0.375, 0.75, 1.5 and 3 mg·kg^-1） was given, the doses of ouabain inducing a variety of arrhythmia PVC, VT, VF, cardiac arrest （CA） were significantly increased with a dose-dependent manner. In the TJ0711 0.1-30 μmol·L^-1 concentration range, guinea pig right ventricular papillary muscle action potential RP （rest potential）, APA （action potential amplitude） and Vmax （maximum velocity of depolarization） were not significantly affected. APD20, APDs0 and APD90 had a shortening trend but no statistical difference with the increase of TJ0711 concentration. T J0711 has antiarrhythmic effect on the sympathetic nerve excitement and myocardial cell high calcium animal arrhythmia model. Myocardial action potential zero phase conduction velocity and resting membrane potential were not inhibited by T J0711. APD20, APD50 and APD90 were shortened by TJ0711 at high concentration. Its anti- arrhythmic action mechanism may be besides the ac

关 键 词：TJ0711 α Β受体阻断剂 氯化钙 哇巴因 缺血再灌注 动作电位 心律失常 

分 类 号：R965[医药卫生—药理学]