鼻黏膜MAchR所介导的对变应性鼻炎鼻分泌亢进的炎性调控机理研究

项目名称： 鼻黏膜MAchR所介导的对变应性鼻炎鼻分泌亢进的炎性调控机理研究

项目编号： No.81200008

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 李娟

作者单位： 重庆医科大学

项目金额： 23万元

中文摘要： 鼻分泌亢进是变应性鼻炎的主要特征，严重影响人们的工作与生活质量。本室前期研究显示，M受体亚型选择性拮抗药苯环喹溴铵可明显减少变应性鼻炎模型模型动物的鼻黏膜腺体分泌；减少嗜酸性粒细胞在鼻黏膜组织的趋化，还可降低变应性鼻炎模型豚鼠鼻黏膜的组胺含量，拮抗组胺（histamine）所诱发的鼻分泌亢进。提示M受体拮抗剂对变应性鼻炎鼻分泌亢进的缓解作用，可能不止限于对鼻黏膜下腺体和血管的直接抗胆碱作用；还牵涉到诸如组胺等其他一些抗炎作用机制。研究表明，支配呼吸道黏膜下腺体的M胆碱受体激动后，可通过PLC 及PKC 途径促进黏蛋白的合成和分泌；而鼻黏膜黏蛋白MUC5AC的表达则可能涉及到p38MAPK、NF-κB、MMP-9等上游信号调控分子的激活。但由M受体所介导的变应性鼻炎鼻分泌亢进的具体机制如何，目前国内外尚未开展深入研究。因此本研究旨在探明，由M受体所介导的对变应性鼻炎鼻分泌亢进的炎性调控机理。

中文关键词： 变应性鼻炎；毒蕈碱受体；鼻分泌亢进；调控机理；MUC5AC

英文摘要： Nasal hypersecretion is the major characteristics of allergic rhinitis, which seriously influence the quality of people's common life.In our early study, bencycloquidum bromide, a subtype-selective muscarinic receptor antagonist, can significantly reduce the quantity of nasal secretion,the migration of eosinophil in nasal mucosa and the content of histamine in allergic rhinitis animals. Moreover, it can antagonize the hypersecretion induced by histamine.So it was suggested that some other anti-inflammatory effect may be involved in the mechanism of muscarinic antagonist on the nasal hypersecretion besides the direct anticholinergic effect. It was demonstrated that the activation of muscarinic receptor on the gland of mucosa can promote the synthesis and secretion of mucoprotein by the pathway of PLC and PKC, while the expression of MUC5AC in nasal mucosa may be induced by the activation of the upstream signaling transduction molecules such as p38MAPK,NF-κB and MMP-9. Nowadays, there was no investigation on the mechanism of nasal hypersecretion mediated by muscarinic receptor in allergic rhinitis. Therefore, in order to provide the theoretical and experimental evidence for the development of new drugs using for the therapy of nasal hypersecretion in allergic rhinits, we plan to investgate the inflammatory mechan

英文关键词： allergic rhinitis；muscarinic receptor；nasal hypersecretion；regulatory mechanism；muc5ac