利尿钠肽系统在心力衰竭中的研究进展

Natriuretic Peptide System in the Therapeutic Applications of Heart Failure

心力衰竭是复杂的多因素综合征,是由心肾功能受损引发的心血管系统疾病,占据心血管疾病死亡原因的首位。利尿钠肽系统(natriuretic peptide system,NPS)在心肾生理调控、体液稳态和代谢调节中发挥着不可或缺的作用,是心力衰竭治疗药物众多研究领域之一。NPS由利尿钠肽及其受体组成,其中利尿钠肽主要包含心房利尿钠肽(atrial natriuretic peptide,ANP)、脑钠肽(brain natriuretic peptide,BNP)和C型利尿钠肽(C-type natriuretic peptide,CNP)等,其受体为利尿钠肽受体A(natriuretic peptide receptor A,NPR-A)、利尿钠肽受体B(natriuretic peptide receptor B,NPR-B)和利尿钠肽受体C(natriuretic peptide receptor C,NPR-C)。利尿钠肽通过与相应的受体结合激活下游环磷酸鸟苷(cyclic guanosine monophosphate,cGMP)信号通路,引起利钠利尿、舒张血管、抗心肌肥大和抗纤维化等生理效应,使心力衰竭患者获益。本文阐述利尿钠肽家族主要成员及其受体的分布情况和结构特征,介绍NPS的信号传导机制和清除途径,总结心力衰竭治疗中靶向NPS的生物药临床现状,包括内源利尿钠肽、重组利尿钠肽及单克隆抗体,为心力衰竭药物的研发提供新思路。

Heart failure(HF)is a complex,multifactorial syndrome resulting from impaired heart and kidney function,which is the leading cause of death in cardiovascular patients.The natriuretic peptide system(NPS)plays an important role in the physiological regulation of heart and kidney,humoral homeostasis,and metabolic regulation,making it one of the numerous research fields in the treatment of HF.The natriuretic peptide(NP)family consists of three biologically active peptides:atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)and C⁃type natriuretic peptide(CNP).There are three natriuretic peptide receptors,including natriuretic peptide receptor⁃A(NPR⁃A),natriuretic peptide receptor⁃B(NPR⁃B)and natriuretic peptide receptor⁃C(NPR⁃C).NPs bind to corresponding receptors and exert physiological effects through increases in intracellular cyclic guanosine monophosphate(cGMP),inhibiting cardiac remodeling and fibrosis.This review introduces the structure,distribution and signaling mechanisms of NPS.In addition,the clinical biological drugs targeting NPS in HF therapies were summarized,including endogenous NPs,recombinant NPs and monoclonal antibodies.