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
网络出版日期: 2015-09-30
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
Online published: 2015-09-30
Supported by
Project of Shenyang Medical College, F14-158-9-23; Scientific Research Foundation of Shenyang Medical College, 200323
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-α 单克隆抗体;变应性鼻炎;NF-κ B信号通路
唐桥斐 , 张爽 , 程阳 , 等 . 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[J]. 上海交通大学学报(医学版), 2015 , 35(9) : 1270 . DOI: 10.3969/j.issn.1674-8115.2015.09.006
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.
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