利钠肽系统干预药物的研发与临床应用

doi:10.3969/j.issn.1674-8115.2026.03.013

摘要/Abstract

摘要：

利钠肽系统是心力衰竭病理生理过程中关键的内源性保护角色。心肌细胞在牵张等刺激下会反应性表达并分泌利钠肽，后者可通过利钠肽受体激活下游信号通路，发挥利钠利尿、扩张血管等一系列生理作用，最终经由利钠肽清除受体或水解酶将其从循环中清除。该级联通路为心力衰竭治疗提供了多个可干预的靶点，涉及利钠肽的合成、受体激活、信号转导以及降解全路径。其中，部分治疗策略已取得了显著的临床进展：重组人利钠肽类药物已被部分国家和地区的心力衰竭指南或共识作为急性心力衰竭的推荐用药；沙库巴曲缬沙坦作为脑啡肽酶抑制剂与血管紧张素Ⅱ受体拮抗剂的复方制剂，已成为国际上治疗射血分数降低型心力衰竭（heart failure with reduced ejection fraction，HFrEF）的标准方案；利钠肽受体激动剂也已进入临床试验阶段且显示出了潜在的治疗前景。基于上述进展，该综述聚焦利钠肽系统干预药物的临床应用与研发，系统梳理不同干预环节相关药物的临床证据与研究进展，以期为心力衰竭治疗策略的优化提供参考。

关键词: 利钠肽, 心力衰竭, 沙库巴曲缬沙坦

Abstract:

The natriuretic peptide system plays a key endogenous protective role in the pathophysiological process of heart failure. Cardiomyocytes reactively express and secrete natriuretic peptides in response to stimuli such as myocardial stretch. These peptides activate downstream signaling pathways through natriuretic peptide receptors, exerting a series of physiological effects including natriuresis and vasodilation, and are ultimately cleared from the circulation via natriuretic peptide clearance receptors or hydrolases. This cascade pathway provides multiple intervention targets for heart failure treatment, covering the entire process of natriuretic peptide synthesis, receptor activation, signal transduction, and degradation. Among these, some therapeutic strategies have achieved significant clinical progress: recombinant human natriuretic peptide drugs have been recommended as treatment options for acute heart failure in the guidelines or consensus statements of some countries and regions; sacubitril/valsartan, a fixed-dose combination of a neprilysin inhibitor and an angiotensin Ⅱ receptor antagonist, has become the international standard treatment regimen for heart failure with reduced ejection fraction (HFrEF); natriuretic peptide receptor agonists have also entered clinical trials and exhibited promising therapeutic potential. Based on these advances, this review addresses the clinical application and development of drugs targeting the natriuretic peptide system, and systematically summarizes the clinical evidence and research progress of agents acting at different intervention nodes, so as to inform the optimization of therapeutic strategies for heart failure.

Key words: natriuretic peptide, heart failure, sacubitril/valsartan

中图分类号:

R972

陈天懿, 贾康妮, 闫小响, 张瑞岩. 利钠肽系统干预药物的研发与临床应用[J]. 上海交通大学学报（医学版）, 2026, 46(3): 385-390.

Chen Tianyi, Jia Kangni, Yan Xiaoxiang, Zhang Ruiyan. Development and clinical application of natriuretic peptide system-targeted drugs[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(3): 385-390.

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