理解鼻息肉病：离子通道、炎症、离子细胞和前列腺素E2的作用——I3PGE2假说

文献信息

中文摘要

鼻息肉病是一种多因素疾病，由细胞、分子和炎症机制之间复杂的相互作用引起。囊性纤维化跨膜传导调节因子（CFTR）和其他离子通道对于鼻气道中的上皮离子转运、黏膜水化和屏障完整性至关重要。前列腺素E2（PGE2）不仅作为炎症介质，还通过CFTR依赖性和CFTR非依赖性途径调节离子交换。离子细胞是调节呼吸道离子平衡和液体分泌的特化上皮细胞，与CFTR功能密切相关。嗜酸性和非嗜酸性炎症均可能改变离子细胞的数量和功能，从而降低正常的CFTR活性。慢性鼻窦炎伴鼻息肉（CRSwNP）的特征还包括PGE2产生减少。I3PGE2假说提出，CRSwNP是离子通道功能障碍、持续性炎症、离子细胞数量和功能改变以及PGE2合成受损共同作用的结果。这些异常共同破坏鼻腔生理并促进息肉形成。我们假设，皮质类固醇和生物制剂可能通过减少炎症、恢复离子通道活性、改善离子细胞功能和恢复PGE2产生来改善CRSwNP。这些效应增强水化和黏液纤毛清除，限制黏液积聚，恢复上皮稳态和黏膜宿主防御，并最终有助于鼻息肉的缩小或消退。

英文摘要

Nasal polyposis is a multifactorial disorder arising from complex interactions among cellular, molecular, and inflammatory mechanisms. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and other ion channels are essential for epithelial ion transport, mucosal hydration, and barrier integrity in the nasal airway. Prostaglandin E2 (PGE2) acts not only as an inflammatory mediator but also as a regulator of ion exchange through CFTR-dependent and CFTR-independent pathways. Ionocytes, specialized epithelial cells that regulate ion balance and fluid secretion in the respiratory tract, are closely associated with CFTR function. Both eosinophilic and non-eosinophilic inflammation may alter ionocyte abundance and function, thereby reducing normal CFTR activity. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also characterized by diminished PGE2 production. The I3PGE2 hypothesis proposes that CRSwNP results from the combined effects of ion channel dysfunction, persistent inflammation, altered ionocyte number and function, and impaired PGE2 synthesis. Together, these abnormalities disrupt nasal physiology and promote polyp formation. We hypothesize that corticosteroids and biologic therapies may improve CRSwNP by reducing inflammation, restoring ion channel activity, improving ionocyte function, and recovering PGE2 production. These effects enhance hydration and mucociliary clearance, limit mucus accumulation, restore epithelial homeostasis and mucosal host defense, and ultimately contribute to the reduction or resolution of nasal polyps.