低氧诱导鼻黏膜上皮细胞释放高迁移率族蛋白1促进上皮屏障损伤  

High mobility group box1 contributes to hypoxia-induced barrier dysfunction of nasal epithelial cells

作　　者：郑静[1] 魏欣[1] 粘家斌[1] 姜鸿彦[1] ZHENG Jing WEI Xin ZHAN Jiabin JIANG Hongyan(Department of Otolaryngology Head and Neck Surgery, Hainan Provincial People＇s Hospital, Haikou, 570311, China)

机构地区：[1]海南省人民医院耳鼻咽喉头颈外科,海口570311

出　　处：《临床耳鼻咽喉头颈外科杂志》2017年第15期1178-1181,共4页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：国家自然科学基金(No:81200732);广东省自然科学基金(No:S2012040006823);广州市属高校"羊城学者"青年科研骨干培养项目(No:1201581626);海南省重点研发项目(No:ZDYF2017115)

摘　　要：目的:研究低氧对鼻黏膜上皮细胞释放高迁移率族蛋白1(HMGB1)的影响,并探讨HMGB1对鼻黏膜上皮屏障的调控作用。方法:取鼻中隔偏曲患者鼻黏膜上皮细胞进行原代培养,观察低氧条件下HMGB1的释放情况。用外源性HMGB1刺激鼻黏膜上皮细胞,检测细胞对异硫氰酸荧光素标记的葡聚糖4(FD4)通透性的影响;并通过Western blot检测上皮连接蛋白(ZO-1、Occcudin、Claudin-1和E-cadherin)的表达。结果:在低氧条件下,鼻黏膜上皮细胞释放HMGB1明显增多。HMGB1呈浓度和时间依赖效应显著增高上皮细胞对FD4的通透性;此外,上皮细胞紧密连接蛋白ZO-1、Occcudin和Claudin-1表达减少,提示上皮屏障功能受损。黏附连接蛋白E-cadherin表达无明显变化。结论:低氧通过促进鼻黏膜上皮细胞释放HMGB1,诱导黏膜上皮屏障损伤,可能在慢性鼻-鼻窦炎的发病中起重要作用。Objective：To investigated the promotion of high mobility group boxl （HMGB1） under hypoxia, and determined the regulatory role of HMGB1 on the barrier function of nasal epithelial celis. Method： Primary na sal epithelial cells（NECs） collected from patients with septal deviation were cultured at air-liquid interface. The release of HMGB1 under hypoxia was detected by EIASA. The effect of HMGB1 on fluorescein isothiocyanate- dextran 4 kDa（FD4） permeability of NECs was measured. Western blot analysis was utilized to examine the level of major junction proteins, namely E-cadherin, ZO-1, Occludin and Claudin-1. Result：The release of HMGB1 was significantly upregulated in NECs under hypoxia. Recombinant human HMGB1 increased FD4 permeability in a dose and time-dependent manner, indicating, the impaired epithelial barrier function. HMGB1 mediated barrier hy perpermeability was accompanied by the selective downregulation of ZO 1, occludin and Claudin-1, but not E-cad herin. Conclusion： HMGB1 mediates hypoxia induce barrier dysfunction of nasal epithelium, which may be a poten- tim target for the treatment of chronic rhinosinusitis

关 键 词：低氧 高迁移率族蛋白1 上皮屏障 鼻窦炎 

分 类 号：R765.4[医药卫生—耳鼻咽喉科]