正性肌力药物作用靶点的研究进展

Progress in research of the targets for inotropic agents

正性肌力药物能影响心肌收缩力,是治疗心力衰竭的主要药物之一,用于治疗心力衰竭的药物疗效及用药患者终期生存率取决于作用靶点。与心肌收缩力有关的靶点包括:β肾上腺素受体、磷酸二酯酶、L-型钙通道、蛋白激酶A、蛋白激酶C、蛋白磷酸酶、Na+-Ca2+交换体、Na+-K+-ATP酶、肌浆网钙泵、受磷蛋白、兰尼碱受体、三磷酸肌醇受体、与钙增敏剂相关的心肌收缩蛋白等。文中对心肌收缩力相关的作用靶点进行综述,分析临床现今使用的和未来的正性肌力药物应具备的靶点特征。

Inotropic drugs affect cardiac muscle contraction and serve as a major clinical treatment of heart failure. The efficacy and terminal survival rate after inotropic drug therapy depend on the targets （or the mechanisms of action） in cardiomyocytes. The targets mediating cardiac muscle contraction include many hiomolecules, such as β-adrenergic receptor, phosphodiesterase （PDE）, L-type calcium channel, protein kinase （PKA）, PKC, protein phosphatase, Na ＋-Ca^2 ＋ exchanger （NCX） , Na ^＋-K ^＋-ATPase, sarcoplasmic reticulum calcium adenosine triphosphatase 2α （SERCA2α）, phospholamban （PLB）, ryanodine receptor （RyRs）, inositol triphosphate receptor （IP3 receptor） , contractile protein related to calcium sensitizer. This paper reviewed the characteristics of the targets to cardiac muscle contractility for new and currently marketed inotropic drugs.