上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

TNF-α单克隆抗体对小鼠变应性鼻炎的治疗作用及机制研究

唐桥斐1，张爽1，程阳2，邰旭辉3，姜玉秋1，闫智永1   

  1. 1．沈阳医学院附属第二医院耳鼻喉科， 沈阳 110002； 2．沈阳医学院病理生理学教研室， 沈阳 110034； 3．解放军第463医院， 沈阳 110042
  • 出版日期:2015-09-28 发布日期:2015-09-30
  • 作者简介:唐桥斐（1977—）， 女， 副主任医师， 硕士; 电子信箱: javawriter@163.com。
  • 基金资助:

    沈阳医学院课题（F14-158-9-23）；沈阳医学院科学研究基金（200323）

Therapeutic effect of TNF-α monoclonal antibody on rats with allergic rhinitis and relevant mechanisms

TANG Qiao-fei1, ZHANG Shuang1, CHENG Yang2, TAI Xu-hui3, JIANG Yu-qiu1, YAN Zhi-yong1   

  1. 1.Department of ENT, the Second Affiliated Hospital of Shenyang Medical College， Shenyang 110002， China； 2.Department of Pathophysiology， Shenyang Medical College, Shenyang 110034， China； 3.PLA 463 Hospital of Shenyang Military Command, Shenyang 110042, China
  • Online:2015-09-28 Published:2015-09-30
  • Supported by:

    Project of Shenyang Medical College, F14-158-9-23; Scientific Research Foundation of Shenyang Medical College, 200323

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摘要：

目的  探讨TNF-α抗体干预对小鼠变应性鼻炎（AR）的治疗作用及潜在分子机制。方法  18只BALB/c小鼠随机分为正常对照组、AR模型组和TNF-α抗体干预组；采用卵清蛋白诱导致敏建立AR模型，于鼻腔刺激前滴加TNF-α单克隆抗体进行治疗；对各组小鼠进行行为学评分，H-E染色观察鼻黏膜组织病理学变化，TUNEL法检测细胞凋亡，ELISA检测鼻黏膜液中TNF-α、IL-1β、IgE表达水平，Western blotting检测NF-κB p65、IκB及凋亡相关蛋白表达变化。结果  TNF-α抗体干预组变应性鼻炎症状减轻，炎症反应程度降低，鼻黏膜液中TNF-α、IL-1β、IgE含量及鼻黏膜组织中NF-κB p65、cleaved caspase-3、Bax表达水平较AR模型组显著降低，I-κB及Bcl-2表达增加。结论  TNF-α单克隆抗体干预对小鼠变应性鼻炎具有一定的治疗作用，可能通过抑制NF-κB信号通路激活、调节Th1/Th2平衡、降低炎性因子水平、抑制细胞凋亡发挥作用。

关键词: TNF-&alpha, 单克隆抗体；变应性鼻炎；NF-&kappa, B信号通路

Abstract:

Objective  To explore the therapeutic effect of the intervention of TNF-α monoclonal antibody on rats with allergic rhinitis (AR) and the underlying molecular mechanism. Methods  Eighteen BALB/c rats were randomly divided into the control group, AR model group, and TNF-α antibody intervention group. The ovalbumin (OVA) induced AR model was established and TNF-α monoclonal antibody was dropped nasally before nasal cavity was stimulated. Behavioral scores of mice were obtained and histopathologic changes of nasal mucosa were observed by H-E staining. The apoptosis of cells was detected by the TUNEL method. Expression levels of TNF-α, IL-1β, and IgE in nasal mucosa fluid were detected with ELISA. Changes of expressions of NF-κB p65, IκB, and apoptosis-related proteins were measured by Western blotting. Results  Symptoms of AR and inflammatory response of the TNF-α antibody intervention group alleviated. Compared with the AR model group, expression levels of TNF-α, IL-1β, and IgE in nasal mucosa fluid and NF-κB p65, cleaved caspase-3, and Bax in nasal mucosa tissues decreased significantly, but expression levels of IκB and Bcl-2 increased. Conclusion  The intervention of TNF-α monoclonal antibody has certain therapeutic effect on rats with allergic rhinitis by inhibiting the activation of NF-κB signaling pathway, regulating Th1/Th2 balance, decreasing expression levels of inflammatory factors, and inhibiting apoptosis of cells.

Key words: TNF-&alpha, monoclonal antibody, allergic rhinitis, NF-κB signaling pathway