p38丝裂原激活蛋白激酶通路对变应性鼻炎中黏蛋白5AC的信号转导机制初探  

A preliminary study on the regulation mechanism of p38MAPK on MUC5AC in allergic rhinitis

作　　者：王振霖[1] 李鹏[2] 李源[2] 张秋航[1] 曲秋懿[1] 齐岩[1] 

机构地区：[1]首都医科大学宣武医院耳鼻咽喉-头颈外科,北京100053 [2]中山大学附属第三医院耳鼻咽喉-头颈外科

出　　处：《临床耳鼻咽喉头颈外科杂志》2011年第20期943-946,共4页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：北京市自然科学基金项目(No:7113156);国家自然科学基金项目(No:81170894)

摘　　要：目的:探讨组胺诱导的离体鼻黏膜组织中,p38丝裂原激活蛋白激酶(p38MAPK)信号通路及环氧合酶-2(COX-2)对黏蛋白5AC(MUC5AC)表达的影响,以期阐明变应性鼻炎(AR)中黏液过度分泌的病理学机制。方法:应用Western blot技术检测不同浓度梯度的组胺诱导及p38MAPK特异性抑制剂SB203580或COX-2特异性抑制剂NS-398干预前后,体外培养的鼻黏膜组织中p38MAPK、COX-2和MUC5AC的蛋白质表达变化规律。结果:p38MAPK、COX-2和MUC5AC在体外培养的健康鼻黏膜组织中呈微弱表达。组胺呈浓度依赖性诱导鼻黏膜组织中p38MAPK、COX-2和MUC5AC蛋白质表达增加;以不同浓度梯度的NS-398阻断COX-2后,观察到NS-398呈浓度依赖性减弱组胺对MUC5AC蛋白质表达的诱导,对p38MAPK表达无明显影响。以不同浓度梯度的SB203580阻断p38MAPK后,观察到SB203580呈浓度依赖性减弱组胺对COX-2和MUC5AC蛋白质表达的诱导。培养液中单独加入SB203580或NS-398对MUC5AC的蛋白质表达无明显影响。结论:组胺通过诱导p38MAPK/COX-2信号途径调节MUC5AC的表达增高可能是AR中黏液过度分泌的部分机制。Objective：To detect the effect of p38 mitogen activated protein kinase（p38MAPK） and cyclooxygenase-2（COX-2） on the expression of mucin5AC（MUC5AC） in human nasal mucosa induced by histamine in vitro,and to investigate the pathogenesis of mucus hypersecretion in allergic rhinits（AR）.Method：Western blot was performed to detect the protein expressions of p38MAPK,COX-2 and MUC5AC in nasal mucosa induced by histamine or blocked by selective inhibitors of p38MAPK and COX-2 of different concentration gradient.Result：Weak expressions of p38MAPK,COX-2 and MUC5AC were detected in normal nasal mucosa in vitro.The protein expressions of p38MAPK,COX-2 and MUC5AC increased in nasal mucosa induced by histamine in a dose-dependent manner.The histamine-induced protein expressions of COX-2 and MUC5AC were dose-dependently attenuated by selective inhibitor of COX-2,namely NS-398.No apparent influence of NS-398 on the expression of p38MAPK was observed.The histamine-induced protein expressions of p38MAPK,COX-2 and MUC5AC dose-dependently decreased after nasal mucosa was treated by selective inhibitor of p38MAPK,namely SB203580.And no significant change of MUC5AC protein expression induced by NS-398 or SB203580 was observed.Conclusion：Our findings indicated that the histamine-induced increased expression of MUC5AC by activated p38MAPK/COX-2 may be a possible pathogenesis of mucus hypersecretion in AR.

关 键 词：鼻炎 变应性 P38丝裂原激活蛋白激酶 环氧合酶-2 黏蛋白 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]