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

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

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、Ig E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、Ig E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。

Objective T o explore the therapeutic effect of the intervention of T N F-α monoclonal antibody on rats w ith allergic rhinitis（ AR） and the underlying m olecular m echanism.Methods Eighteen BALB / c rats w ere random ly divided into the control group,AR m odel group,and T N F-α antibody intervention group.T he ovalbum in（ O V A） induced AR m odel w as established and T N F-α m onoclonal antibody w as dropped nasally before nasal cavity w as stim ulated.Behavioral scores of m ice w ere obtained and histopathologic changes of nasal m ucosa w ere observed by H-E staining.T he apoptosis of cells w as detected by the T U N EL m ethod.Expression levels of T N F-α,IL-1β,and Ig E in nasal m ucosa fluid w ere detected w ith ELISA.C hanges of expressions of N F-κB p65,IκB,and apoptosis-related proteins w ere m easured by W estern blotting.Results Sym ptom s of AR and inflam m atory response of the T N F-α antibody intervention group alleviated.C om pared w ith the AR m odel group,expression levels of T N F-α,IL-1β,and Ig E in nasal m ucosa fluid and N F-κB p65,cleaved caspase-3,and Bax in nasal m ucosa tissues decreased significantly,but expression levels of IκB and Bcl-2increased.Conclusion T he intervention of T N F-α m onoclonal antibody has certain therapeutic effect on rats w ith allergic rhinitis by inhibiting the activation of N F-κB signaling pathw ay,regulating T h1 / T h2 balance,decreasing expression levels of inflam m atory factors,and inhibiting apoptosis of cells.