Wang Hong, Wu Jing, Zhang Ruxin
Department of Otorhinolaryngology, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Am J Rhinol Allergy. 2023 Nov;37(6):730-738. doi: 10.1177/19458924231191012. Epub 2023 Jul 31.
Neurokinin-1 receptor (NK-1R) and normal T cell expressed and secreted (RANTES) have been shown to play important roles in allergic rhinitis (AR). However, whether the regulating effect of NK-1R in AR is achieved via RANTES remains unknown.
In the present study, Sprague-Dawley rats were sensitized and challenged with ovalbumin to make AR models. During the challenge period, the rats were treated intranasally with NK-1R-specific small interfering RNA (siRNA) for NKR group, negative siRNA for NCS group, rats in NSAR group and NS group were given saline. The amount of nasal secretion and the numbers of nose rubs and sneezes were measured in each rat. The levels of NK-1R and RANTES in the nasal mucosal tissues were determined through real-time fluorescence quantitative RT-PCR and immunohistochemical staining. The numbers of eosinophils in the collected nasal lavage fluid (NLF) were counted, and the concentration of RANTES in NLF was determined by enzyme-linked immunosorbent assay.
Compared with that in the NS group, the expression of NK-1R and RANTES was significantly higher in the nasal mucosa of NSAR and NCS group rats. The sneezing and nose rubbing counts and the amount of nasal secretions were increased significantly in the NSAR and NCS groups. Rats in the NKR group experienced greater relief from AR symptoms than rats in the NSAR and NCS groups. Furthermore, knockdown of NK-1R expression also significantly eliminated RANTES expression and eosinophil infiltration in the nasal mucosa of NKR group rats.
For the first time, we show that intranasal treatment with NK-1R-specific siRNA can significantly decrease RANTES expression, AR-related symptoms, and eosinophil inflammation, suggesting that the regulating effect of NK-1R in the development of AR occurs via alteration of RANTES expression.
神经激肽-1受体（NK-1R）和正常T细胞表达和分泌因子（RANTES）已被证明在变应性鼻炎（AR）中起重要作用。然而，NK-1R在AR中的调节作用是否通过RANTES实现仍不清楚。
在本研究中，用卵清蛋白对Sprague-Dawley大鼠进行致敏和激发以建立AR模型。在激发期，NKR组大鼠经鼻给予NK-1R特异性小干扰RNA（siRNA），NCS组给予阴性siRNA，NSAR组和NS组大鼠给予生理盐水。测量每只大鼠的鼻分泌物量、蹭鼻和打喷嚏次数。通过实时荧光定量RT-PCR和免疫组化染色测定鼻黏膜组织中NK-1R和RANTES的水平。计数收集的鼻灌洗液（NLF）中的嗜酸性粒细胞数量，并通过酶联免疫吸附测定法测定NLF中RANTES的浓度。
与NS组相比，NSAR组和NCS组大鼠鼻黏膜中NK-1R和RANTES的表达明显更高。NSAR组和NCS组的打喷嚏和蹭鼻次数以及鼻分泌物量显著增加。NKR组大鼠的AR症状缓解程度比NSAR组和NCS组大鼠更大。此外，NK-1R表达的敲低也显著消除了NKR组大鼠鼻黏膜中RANTES的表达和嗜酸性粒细胞浸润。
我们首次表明，经鼻给予NK-1R特异性siRNA可显著降低RANTES表达、AR相关症状和嗜酸性粒细胞炎症，提示NK-1R在AR发生发展中的调节作用是通过改变RANTES表达实现的。
