Duan Chen, Ma Xinyi, Liu Fangying, Xie Xinyu, Wu Changhua, Zhang Xiaojun, Ye Ping, Yuan Ye, Feng Xin
Department of Otorhinolaryngology, Qilu Hospital of Shandong University, National Health Commission Key Laboratory of Otorhinolaryngology (Shandong University), Shandong Provincial Key Medical and Health Discipline of Qilu Hospital of Shandong University, Jinan, People's Republic of China.
J Inflamm Res. 2025 Apr 16;18:5097-5109. doi: 10.2147/JIR.S504050. eCollection 2025.
Olfactory dysfunction (OD) in allergic rhinitis (AR) significantly diminishes quality of life, yet its pathophysiology remains unclear. The Notch signaling pathway is known to regulate olfactory epithelium proliferation and differentiation in murine models, but its role in AR with OD (AR+OD) is yet to be elucidated. This study aims to explore neuronal expression patterns and the involvement of Notch signaling in AR+OD.
Symptom severity of 111 AR patients, 65 non-AR patients, and controls was evaluated according to the SNOT-22 criteria. Olfactory dysfunction in an AR mouse model was assessed via the Buried Food Pellet Test (BFPT). Immunofluorescence, H&E staining, ELISA, and PCR techniques were employed to detect inflammation and olfactory epithelium in AR+OD, AR without OD (AR-OD), and control groups. DAPT, a Notch signaling inhibitor, was administered to assess its therapeutic potential in OD of AR.
AR patients had higher sneezing, rhinorrhea, nasal itching, nasal congestion and olfactory scores, but no correlation was found between nasal congestion and olfactory dysfunction. Significant increases in the symptom scores, eosinophil infiltration, OVA-specific IgE levels and worse olfactory function were observed in the AR mice model compared to the Control group. In particular, AR+OD mice group exhibited thinner olfactory epithelium, increased immature neuron expression, decreased mature neurons, and upregulated Notch expression as compared to AR-OD group. DAPT treatment significantly enhanced olfactory mature neuron expression and improved OD of AR mice.
Our research indicates that impaired differentiation of olfactory neurons may contribute to the underlying causes of olfactory dysfunction in AR. Additionally, inhibiting the Notch signaling pathway promotes the maturation of the olfactory epithelium and improves olfactory dysfunction in AR mice, offering potential therapeutic strategies for olfactory disorders in AR.
变应性鼻炎（AR）中的嗅觉功能障碍（OD）会显著降低生活质量，但其病理生理学仍不清楚。已知Notch信号通路在小鼠模型中调节嗅觉上皮细胞的增殖和分化，但其在伴有OD的AR（AR+OD）中的作用尚待阐明。本研究旨在探讨Notch信号在AR+OD中的神经元表达模式及参与情况。
根据SNOT-22标准评估111例AR患者、65例非AR患者和对照组的症状严重程度。通过埋食颗粒试验（BFPT）评估AR小鼠模型中的嗅觉功能障碍。采用免疫荧光、苏木精-伊红染色、酶联免疫吸附测定（ELISA）和聚合酶链反应（PCR）技术检测AR+OD组、无OD的AR（AR-OD）组和对照组中的炎症和嗅觉上皮情况。给予Notch信号抑制剂DAPT以评估其对AR的OD的治疗潜力。
AR患者的打喷嚏、流涕、鼻痒、鼻塞和嗅觉评分较高，但鼻塞与嗅觉功能障碍之间未发现相关性。与对照组相比，AR小鼠模型的症状评分、嗜酸性粒细胞浸润、卵清蛋白特异性IgE水平显著增加，嗅觉功能更差。特别是，与AR-OD组相比，AR+OD小鼠组的嗅觉上皮更薄，未成熟神经元表达增加，成熟神经元减少，Notch表达上调。DAPT治疗显著增强了AR小鼠嗅觉成熟神经元的表达并改善了其OD。
我们的研究表明，嗅觉神经元分化受损可能是AR中嗅觉功能障碍的潜在原因。此外，抑制Notch信号通路可促进嗅觉上皮成熟并改善AR小鼠的嗅觉功能障碍，为AR中的嗅觉障碍提供了潜在的治疗策略。
