卡维地洛与培哚普利联合干预心梗后心衰对心肌肌浆网Ca^(2+)泵活性和Ca^(2+)释放通道密度的影响

Effect of carvedilol and perindopril on Ca^(2+) pump activity and Ca^(2+)-release channel density in myocardial sarcoplasmic reticulum in rats with chronic heart failure following myocardial infarction

目的探讨β受体阻滞剂卡维地洛与血管紧张素转换酶抑制剂培哚普利联合干预心梗后慢性心衰对心肌肌浆网(SR)Ca2+泵活性和Ca2+释放通道(RyR2)密度的影响及意义。方法通过结扎大鼠左冠脉建立慢性心衰模型,术后1周开始分别给以卡维地洛(6mg·kg-1·d-1)、培哚普利(4mg·kg-1·d-1)、特拉唑嗪(2mg·kg-1·d-1)、卡维地洛(6mg·kg-1·d-1)+培哚普利(4mg·kg-1·d-1)联合干预9周,观察血流动力学、左室心肌SRCa2+泵活性和RyR2密度的变化。结果与假手术组相比,心衰组左室舒张末压(LVEDP)显著升高(P<0.01),+dp/dtmax、-dp/dtmax显著降低(P<0.01),左室心肌SRCa2+泵活性和RyR2密度显著降低(P<0.01)。卡维地洛、培哚普利单独及联合干预均降低LVEDP(P<0.01),升高+dp/dtmax、-dp/dtmax(P<0.01),并升高左室心肌SRCa2+泵活性和RyR2密度(P<0.01),联合干预变化更明显(P<0.01)。特拉唑嗪组对上述指标无明显影响(P>0.05)。左室心肌SRCa2+泵活性与+dp/dtmax、-dp/dtmax显著正相关(r=0.596,r=0.684,P<0.01)。结论β受体阻滞剂卡维地洛和血管紧张素转换酶抑制剂培哚普利长期联合干预心梗后慢性心衰,能够改善血流动力学和心肌SRCa2+泵活性,增加RyR2密度,优于任何单一药物干预。

Objective To study the effects of carvedilol combined with perindopril on Ca2+ pump activity and the density of Ca2+-release channel ryanodine receptor(RyR2) in the myocardial sarcoplasmic reticulum(SR) in rats with chronic heart failure caused by myocardial infarction.Methods Rat models of chronic heart failure established by left coronary artery ligation were divided into different groups and treated with carvedilol(6 mg·kg-1·d-1),perindopril(4 mg·kg-1·d-1),terazosin(2 mg·kg-1·d-1),or the combination of c...