神经肽Y受体调节剂在肠道生理和治疗中的应用

摘要(中文译文)

肠脑通讯依赖于神经肽和激素，其中神经肽Y（NPY）家族，包括NPY、肽YY（PYY）和胰多肽（PP），发挥着重要作用。这些肽还影响胃肠（GI）动力、分泌、营养吸收和肠道发育。包括肠易激综合征（IBS）、炎症性肠病（IBD）、胃轻瘫和肥胖在内的疾病，均被归因于该信号轴的紊乱。本综述评估了NPY及其受体亚型（Y1、Y2、Y4、Y5）在胃肠道中的生理和病理功能，以及该通路药理学和天然调节剂的治疗潜力。本文对近期实验、临床和药理学证据进行了概述，以描述受体特异性活性、阐明潜在病理生理机制，并探讨NPY调控在胃肠道健康和疾病中的临床意义。文献表明，NPY信号通过多种受体途径控制胃肠动力、分泌和食欲。低NPY水平常与IBD的腹泻表现相关，而PYY介导的回肠制动有助于增强营养吸收。新的治疗策略前景可观：Y1受体激动剂可减少腹泻，Y1拮抗剂可用于便秘，Y2/Y5调节剂可能对包括肥胖和胃轻瘫在内的一些病症有用。现有证据证实了NPY受体在胃肠道稳态和疾病病理中所发挥的作用。基于精准的药理学干预模型有助于加深对受体间相互作用的理解。然而，研究设计的差异和长期临床数据的缺乏也是显著的不足。NPY系统是肠脑轴的重要组成部分。抑制Y受体通路是促进胃肠功能并弥合功能性和炎症性胃肠疾病治疗缺口的一种有吸引力的方法。

Abstract

Gut-brain communication depends on neuropeptides and hormones, and the Neuropeptide Y (NPY) family, which includes NPY, Peptide YY (PYY), and Pancreatic Polypeptide (PP), plays an important role. These peptides also affect gastrointestinal (GI) motility, secretion, nutrient uptake, and intestinal development. Diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), gastroparesis, and obesity, are attributed to disruptions in this signaling axis. In this review, the physiological and pathological functions of NPY and its receptor subtypes (Y1, Y2, Y4, Y5) in the GI tract, the therapeutic potential of Pharmacological and natural modulators of this pathway are evaluated. An overview of recent experimental, clinical, and pharmacological evidence was carried out to describe receptor-specific activity, delineate the underlying pathophysiology, and investigate the clinical implications of NPY modulation in gastrointestinal health and disease. Literature reveals that NPY signaling controls GI motility, secretion, and appetite via diverse receptor pathways. Low NPY levels are often linked with diarrheal manifestations of IBD, while PYY-mediated ileal brake supports enhanced nutrient absorption. New therapeutic strategies are promising: Y1 receptor agonists can reduce diarrhoea, Y1 antagonists can be useful in constipation, and Y2/Y5 modulators may be useful in some conditions, including obesity and gastroparesis. The existing evidence confirms the role NPY receptors play in the GI homeostasis and disease pathology. The modeling of precision-based pharmacological interventions facilitates an enhanced comprehension of receptor-based interactions. Yet, the difference in the study design and the paucity of long-term clinical data are also significant weaknesses. The NPY system is an essential part of the gut-brain axis. Inhibition of Y-receptor pathways is an attractive approach to promote GI functionality and bridge therapeutic gaps in functional and inflammatory gastrointestinal diseases.

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