附子中单酯型生物碱类成分靶向ACE2-Ang1-7轴治疗慢性心力衰竭的研究进展

心力衰竭是指心脏无法泵血,除了心脏移植或心室辅助装置外,尚无更有效的治疗方法的一个公共卫生问题.肾素-血管紧张素系统(RAS)在调节正常生理和心血管疾病的发病机制中具有重要作用.血管紧张素转换酶2(ACE2)及其产物血管紧张素1-7(Ang1-7)被认为对其他已知的RAS成员的不良反应具有抵消作用.现代药理学研究发现,单酯型生物碱是附子二萜类双酯型生物碱的水解产物,具有明显降压,抑制心肌收缩力等作用,但其作用机制还有待研究.本文论述了慢性心衰中ACE2、Ang(1-7)的基本特性及其相互关系,探讨了通过靶向ACE2-Ang(1-7)-MAS受体轴从而产生心血管保护作用的机制,总结了近年来附子中单酯型生物碱靶向ACE2-Ang(1-7)-MAS轴的抗心衰作用研究进展,为深入研究心力衰竭以及药物的开发利用提供依据.

Heart failure is a public health problem in which the heart is unable to pump blood and there is no definite treatment except for heart transplantation or ventricular assist devices.The renin-angiotensin system(RAS)plays an important role in regulating the pathogenesis of normal physiology and cardiovascular diseases.Angiotensin converting enzyme 2 (ACE2) and its product angiotensin 1-7 (Ang1-7) have been shown to counteract adverse reactions in other known RAS members.It has been found in modern pharmacology that monoester alkaloid is the hydrolyzed product of aconite diterpene diester alkaloid,which has obvious antihypertensive and myocardial contractile effects,but its mechanism remains to be studied.This article discusses the basic characteristics of ACE2 and Ang (1 -7) and their correlations related to chronic heart failure.The recent advances about targeting the ACE2-Ang (1-7)-MAS receptor axis in the treatment to heart failure by monoester alkaloids of aconite were summarized.The mechanism of targeting the ACE2- Ang (1-7)-MAS axis to produce cardiovascular protection was discussed.This paper will provide a basis for in -depth study of heart failure and the development and utilization of drugs.