NPY-Y1信号通路调控嗜酸粒细胞性慢性鼻窦炎大鼠鼻黏膜嗜酸粒细胞性炎症的机制研究  

Mechanism of NPY-Y1 signaling pathway regulation of eosinophilic inflammation in the nasal mucosa of rats with chronic sinusitis

作　　者：王佳艳 徐明 王伟[1] 贾旭锦 WANG Jiayan;XU Ming;WANG Wei;JIA Xujin(Department of Otolaryngology,Ningbo Traditional Chinese Medicine Hospital Afiliated to Zhejiang Chinese Medicine University,Ningbo,Zhejiang,315000,China)

机构地区：[1]浙江中医药大学附属宁波市中医院耳鼻咽喉科,浙江宁波315000

出　　处：《中国耳鼻咽喉头颈外科》2024年第5期305-310,共6页Chinese Archives of Otolaryngology-Head and Neck Surgery

基　　金：宁波市科技计划项目(2022J281);宁波市医学科技计划项目(2022Y19)。

摘　　要：目的探究NPY-Y1信号通路调控嗜酸粒细胞性慢性鼻窦炎(eosinophilic chronic rhinosinusitis,ECRS)大鼠鼻黏膜嗜酸粒细胞性炎症的机制。方法72只大鼠按照体重随机分组法分为6组,每组各12只,包括对照组、ECRS组、空载组、神经肽Y(NPY)干扰组、低拮抗剂组和高拮抗剂组。除对照组外,其余5组采用卵清蛋白致敏+细菌毒素法构建ECRS大鼠模型,空载组和NPY干扰组分别尾静脉注射siNC和NPY siRNA质粒进行干预,低拮抗剂组和高拮抗剂组分别腹腔注射20、50μg的BIBO 3304干预。末次刺激结束后处死大鼠,取鼻腔黏膜组织,进行HE染色和嗜酸粒细胞(Eos)计数;RT-PCT法检测鼻黏膜中NPY、IL-4、IL-5、IL-13 mRNA表达情况,Western blot法检测核因子κB p65(NF-κB p65)、NF-κB p50蛋白表达情况,免疫组织化学法检测NPY、NPY1受体(Y1R)表达情况。结果HE染色结果显示,对照组鼻黏膜组织结构完整有序,ECRS组、空载组细胞排列紊乱,出现大量炎性细胞浸润,低拮抗剂组中细胞结构得到改善,炎性细胞浸润减少,相对于低拮抗剂组,NPY干扰组、高拮抗剂组中细胞结构及炎性细胞浸润改善情况更显著。与对照组比较,ECRS组和空载组鼻黏膜Eos计数,NPY、IL-4、IL-5、IL-13 mRNA,NF-κB p65、NF-κB p50蛋白及NPY、Y1R细胞染色相对强度值均明显升高(P均<0.05);与ECRS组和空载组比较,NPY干扰组、低拮抗剂组、高拮抗剂组上述指标均降低,且NPY干扰组和高拮抗剂组低于低拮抗剂组(P均<0.05);ECRS组与空载组、NPY干扰组和高拮抗剂组上述指标比较差异无统计学意义(P均>0.05)。结论ECRS大鼠存在鼻黏膜Eos异常浸润炎症反应,其机制可能与NPY-Y1信号通路通过激活NF-κB信号通路及效应蛋白表达有关。OBJECTIVE To investigate the mechanisms by which the NPY-Y1 signalling pathway regulates eosinophilic inf lammation in the nasal mucosa of rats with eosinophilic chronic rhinosinusitis(ECRS).METHODS Seventy-two rats were divided into 6 groups according to the random grouping method of body weight.There were 12 rats in each group,including the control group,ECRS group,no-loading group,neuropeptide Y(NPY)interference group,low antagonist group and high antagonist group.Except for the control group,the ECRS rat model was constructed using the ovalbumin sensitisation+bacterial toxin method in the other five groups.The no-loading group and NPY-interfering group were intervened by tail vein injection of siNC and NPY siRNA plasmid,respectively,and the low and high antagonist groups were intervened by intraperitoneal injection of 20 and 50μg of BIBO 3304,respectively.The rats were executed at the end of the final stimulation,and the nasal mucosal tissues were taken for HE staining and eosinophil(Eos)counting.NPY,IL-4,IL-5,IL-13 m RNA e xpression i n n asal m ucosa w as d etected b y RT-PCT.N uclear factorκB p65(NF-κB p65),NF-κB p50 protein expression was detected by Western blot method.NPY,NPY1 receptor(Y1R)expression was detected by immunohistochemistry.RESULTS HE staining results showed that the tissue structure of the nasal mucosa in the control group was complete and orderly.In the ECRS group and the airborne group,the cell arrangement was disordered and a large number of inflammatory cell infiltration appeared.In the low antagonist group,the cell structure was improved and the inflammatory cell infiltration was reduced.Compared with the low antagonist group,the improvement of cell structure and inflammatory cell infiltration was more significant in the NPY interference group and high antagonist group.Compared with the control group,the Eos count of nasal mucosa,NPY,IL-4,IL-5,IL-13 mRNA,NF-κB p65,NF-κB p50 protein and the relative intensity values of NPY and Y1R cell staining were significantly higher in both t

关 键 词：鼻窦炎 神经肽Y 受体 神经肽Y 鼻黏膜 炎症 大鼠 嗜酸粒细胞性慢性鼻窦炎 

分 类 号：R73[医药卫生—肿瘤]