从视交叉上核到膀胱：精氨酸加压素、肾脏、膀胱与夜尿症

From the suprachiasmatic nucleus to the bladder: AVP, kidney, bladder and nocturia

摘要

在夜尿症发病机制中，精氨酸加压素（AVP）是一个关键性的调控因子，其功能网络涉及昼夜节律调控、肾脏水盐代谢及膀胱储尿三个环节。视交叉上核内的AVP能神经元合成并呈节律性释放AVP，该神经肽不仅是生物钟的重要输出信号，也是维持昼夜节律稳态的关键因子之一。研究表明，AVP节律紊乱可导致其夜间分泌峰值降低或缺失，进而削弱肾脏集合管对尿液的浓缩能力，诱发夜间多尿。在肾脏层面，AVP通过激活集合管主细胞膜上的V2受体，经cAMP/PKA信号通路上调水通道蛋白2的膜表达，从而介导抗利尿效应。需要指出的是，肾脏对AVP反应性下降、肾脏外周生物钟随增龄出现的功能衰退，以及睡眠障碍等因素，均可协同加剧夜尿症状。近年来，膀胱黏膜局部AVP及其受体表达的存在被证实，提示AVP可能以旁分泌方式参与储尿功能的主动调控。综上所述，由AVP昼夜节律、肾脏功能与膀胱储尿功能构成的三环节联合调控网络，为解析夜尿症的多因素发病机制及其治疗反应的个体差异提供了系统框架，并为去氨加压素的精准应用及新型干预策略的研发奠定了理论基础。

Abstract

Arginine vasopressin (AVP) is a key regulator in the pathogenesis of nocturia, acting across three integrated domains: circadian rhythms, renal water-salt handling, and bladder storage. AVP is synthesized and released rhythmically by AVPergic neurons in the suprachiasmatic nucleus (SCN). This neuropeptide acts as both a major output of the central circadian clock and a critical contributor to circadian homeostasis. Disruption of this AVP rhythm reduces or eliminates its nocturnal secretory peak, which impairs urine concentration in the renal collecting duct and drives nocturnal polyuria. At the renal level, AVP exerts its antidiuretic effects by activating the V2 receptor (V2R) on collecting duct principal cells, leading to cAMP/PKA-dependent insertion of aquaporin-2 (AQP2) into the apical membrane. Factors such as decreased renal AVP sensitivity (AVP resistance), age-related decline of the kidney's peripheral circadian clock, and sleep disturbances can synergistically worsen nocturia. Recent evidence also confirms local expression of AVP and its receptors in the bladder mucosa, suggesting a paracrine role for AVP in actively regulating urine storage. Together, this three-node regulatory network-AVP circadian rhythm, renal function, and bladder storage-offers a system-level framework for understanding the multifactorial causes of nocturia and the interindividual variability in treatment response. It also provides a rationale for the precise use of desmopressin and the development of new therapeutic strategies.

关键词

精氨酸加压素 / 夜尿症 / 昼夜节律 / 肾脏 / 膀胱 / 去氨加压素

Key words

arginine vasopressin / nocturia / circadian rhythm / kidney / bladder / desmopressin

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基金资助

国家重点研发计划项目(2023YFC3605303)