摘要
目的通过探究IL^(-1)7A中和抗体缓解慢性鼻窦炎伴鼻息肉(CRSwNP)组织重塑的作用机制,为临床治疗CRSwNP组织重塑寻找新靶点。方法BALB/c小鼠32只,随机分为Control组,C+IL^(-1)7A中和抗体组,HDM模型组,HDM+IL^(-1)7A中和抗体组。ELISA和免疫组化检测小鼠炎症因子的表达。HE着色法察看小鼠鼻息肉及下鼻甲粘膜的病变,Western blot检测小鼠和HNEpCs中MMP-9、VEGF、Act1、Traf6、NF-κB信号通路蛋白。结果CRSwNP小鼠中IL-4、IL^(-1)7A表达水平增加,MMP-9、VEGF、Act1、Traf6、NF-κB信号通路蛋白表达上调,其鼻组织炎症浸润明显,而予以IL^(-1)7A中和抗体后以上蛋白表达水平下降,炎症浸润缓解。IL^(-1)7A刺激HNEpCs后Act1、Traf6、NF-κB信号蛋白表达增加,而予以anti-IL^(-1)7RA和Traf6 inhibitor预处理可降低以上蛋白的表达水平。结论IL^(-1)7A可能在CRSwNP的组织重塑中发挥至关重要的作用。阻滞IL^(-1)7RA/Traf6/NF-κB信号通路可以缓解鼻窦炎伴鼻息肉组织重塑。
Aim To explore the mechanism of IL^(-1)7A neutralizing antibody in alleviating tissue remodeling in chronic rhinosinusitis with nasal polyps(CRSwNP),and to find a new target for clinical treatment of CRSwNP tissue remodeling.Methods 32 BALB/c mice were randomly divided into four groups:Control group,C+IL^(-1)7A neutralizing antibody group,HDM model group and HDM+IL^(-1)7A neutralizing antibody group.ELISA and immunohistochemistry were used to detect the expression of inflammatory factors in mice.HE staining was used to detect the pathological changes of mouse nasal tissue.Western blot was used to detect the expression of MMP-9,VEGF,Act1,Traf6 and NF-κB signaling pathway protein in mice and HNEpCs.Results The expression of IL-4,IL^(-1)7A,MMP-9,VEGF,Act1,Traf6 and NF-κB signaling pathway proteins were up-regulated and the nasal tissue inflammation infiltration was obvious in CRSwNP mice,while the expression levels of the above proteins were decreased and the inflammatory infiltration was relieved after IL^(-1)7A neutralizing antibody was given.The expression of Act1,Traf6 and NF-κB in HNEpCs stimulated by IL^(-1)7A were increased.Pretreatment with anti-IL^(-1)7RA and TRAF6 inhibitor decreased the expression levels of the above proteins.Conclusion IL^(-1)7A may play a crucial role in the tissue remodeling in CRSwNP.Blocking IL^(-1)7RA/TRAF6/NF-κB signaling pathway may alleviate the tissue remodeling of CRSwNP.
作者
王重阳
于洋
金海南
宋艺兰
刘思奇
张雅琳
延光海
金永德
WANG Chong-yang;YU Yang;JIN Hai-nan;SONG Yi-lan;LIU Si-qi;ZHANG Ya-lin;YAN Guang-hai;JIN Yong-de(Key Laboratory of Immunization and Targeted Research on Common Allergic Diseases in Jilin Province,Yanbian University,Yanji Jilin 133002;Department of Otolaryngology, Affiliated Hospital of Yanbian University, Yanji Jilin 133002;Department of Anatomy,Yanbian University School of Medicine,Yanji Jilin 133002)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2021年第10期1416-1421,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(81760185)。
作者简介
王重阳(1991-),女,博士后,研究方向:过敏性疾病,E-mail:m18804331583@163.com;通信作者:金永德(1964-),男,博士,博士生导师,研究方向:过敏性鼻炎,E-mail:jyd0091@126.com;通信作者:延光海(1975-),男,博士,博士生导师,研究方向:过敏性常见疾病免疫与靶向,E-mail:ghyan2015@sina.com。
