目的:研究去甲乌药碱与6-姜酚单体及其配伍对心衰大鼠的强心作用及其机制。方法:结扎大鼠冠脉左前旋降支制作心衰模型,分组为假手术组,模型组,多巴酚丁胺组,去甲乌药碱组,6-姜酚组,配伍组进行不同干预,应用动物超声检测心脏射血分数,使用多通道生理记录仪检测心脏HR、LVSP、LVDEP及±dp/dt变化,并应用Westen blot技术检测钙转运及收缩相关蛋白变化以阐述药物作用机制。结果:模型组动物较假手术组射血分数和心室肌收缩±dp/dt明显降低(P〈0.01)。单独应用去甲乌药碱或6-姜酚不能改善心肌收缩能力,但两者配伍能够增加射血分数和左心室收缩±dp/dt,从而改善心功能。Western blot的研究结果显示,各组雷诺丁受体(RyR2)蛋白表达没有显著性差异;模型组Troponin C(cTnC)、肌浆网钙ATP酶(SERCA2a)较假手术组含量明显降低(P〈0.05,P〈0.01),但各给药组cTnC与模型组比较没有显著性差异;多巴酚丁胺、去甲乌药碱和6-姜酚各自单独用药后SERCA2a表达与模型组比较未见显著差异,而配伍组能够增加心脏SERCA2a表达(P〈0.05)。结论:去甲乌药碱与6-姜酚配伍能够增强心衰大鼠心肌收缩力,其机制为增加心脏SEACA2a蛋白表达,改善收缩和舒张功能。
Objective:To investigate the cardiotonic mechanism of compatibility of higenamine and 6-gingerol on heart failure rat.Methods:Heart failure rat models were established by ligaturing the left anterior descending artery of rats.Rats included in sham operation group,model group,dobutamine group,higenamine group,6-gingerol group and compatibility group were treated with the corresponding intervention measures.The heart ejection fraction was determined by ultrasonic testing.The changes in HR,LVSP,LVDEP and ±dp/dt were tested by using multi-channel physiology recorder.The changes in calciumtransport protein and contraction-associated protein were tested by using western blotting.Results:The ejection fraction and ±dp/dt of ventricular contractility of rats in model group were lower than those of sham operation group.6-gingerol used alone could not improve the ventricular contractility,but compatibility of higenamine and 6-gingerol could increase the ejection fraction and ±dp/dt of left ventricular systole,and improve cardiac function consequently.The results of Western blot showed that the difference in expression of RyR2 in rats among these groups was not significant.The contents of cTnC and SERCA2 a of rats in model group were significantly lower than that of sham operation group(P〈0.05,P〈0.01),but the difference in cTnC among treatment groups and model group was not significant.The difference in expression of SERCA2 of rats among dobutamine group,higenamine group,6-gingerol group and model group was not significant,but the expression of SERCA2 of rats in compatibility group was increased(P〈0.05).Conclusion:Compatibility of higenamine and 6-gingerol could enhance the myocardial contractility of rats with heart failure,and the mechanism was the increasing expression of SEACA2 a in heart,which could improve the systolic and diastolic function.