Expression And Significance Of NF-κB P65in Mice With Allergic Rhinitis

Objective: Allergic rhinitis is a chronic inflammatory disease of nasalmucosa, its pathogenesis is Th1and Th2immune response from theimbalance, with Th2immune response of the inflammatory response asallergic, it show a large Th2cytokines expression of Th cells, eosinophilicacid granulocyte and mast cells infiltration, and cause inflammatory reactionprocess. One of the most important features of the inflammatory process isadhesion of inflammatory cells, then pass through the endothelial cell, andinfiltrate into the inflammation parts. Nuclear transcription factors-κ B(NF-κB) is considered to be the inflammatory response center link, the key ofthe reaction is activation of vascular endothelial cell, the activation ofendothelial cells produce a series of adhesion molecules, cells factor, enzyme,and other media in the NF-κB system's adjustment, those medium aremediated or directly involved in interaction of inflammatory cells and endothelial cell, of which the key link is adhesion of inflammatory cells andendothelial cell, related molecules have Intercellular adhesion molecule-1(ICAM-1) and Vascular cell adhesion molecule-1(VCAM-1). As tissueanatomical and histological similarities of the upper and lower respiratory,inflammatory lesions rarely confined to one area. The upper and the lowerrespiratory tract allergy inflammation often occur at the same time, allergicrhinitis is not only related to asthma, but also a risk factor for asthma. Themice as object of the research is established mice model of allergic rhinitis,endothelial cells as the breakthrough point, research the expression ofNF-kappa B p65and ICAM-1, VCAM-1in the nasal mucosa and lung tissue,then discuss the role of three in the pathogenesis of allergic rhinitis and theinfluence of the airways, so as to provide a new idea for the treatment ofallergic rhinitis. Methods:30FVB mice were randomly divided into control group,allergic rhinitis group (AR group) and hormone intervention group, AR groupconducts the basal sensitization with intraperitoneal injection of10%eggalbumin (ovalbumin, OVA), and then exposed to5%OVA suspensionintranasally, at last Gives5%OVA aerosolized, so as to induce mice model ofallergic rhinitis.Behavioral points is evaluated animal model. hematoxlin-eosin is used to observe morphology change. Immunohistochemical is used toobserve the expression of the NF-κB p65and ICAM-1, VCAM-1in the nasalmucosa and lung tissue. Western blotting test the expression of NF-κB p65and VCAM-1in the lung tissue. Enzyme-linked immunosorbent assay(ELISA) is used to detect IL-4level in peripheral blood. Bronchial lavagefluid centrifugal sedimentation smear used to an acid granulocyte count.SPSS13.0is used to statistical analysis, multi-factor analysis of varianceanalysis was used to process the data, regard α=0.05as the level ofsignificance difference.Results: Models were successfully established in10mice from modelgroup.1.Hematoxlin-eosin is used to observe morphology change:The Control groupand the hormone intervention group had no significant nasal and lunginflammation;Nasal mucosa of model group show different degree oedema,disorder of epithelial cell structure, cup shape cell hyperplasia, infiltration ofsubmucosal eosinophilic acid granulocyte (eosinophils, Eos), lymphocytes andmononuclear cells; bronchial, fine bronchial and alveolar space narrow in themodel lung tissue, alveolar interval broadens, and the wall and pulmonaryintersitital have inflammatory cells infiltrating such as eosinophil; The nasalmucosa of hormone intervention group show complete epithelial, Neat cilia,necrosis of airway epithelial cell lighten to model group, epithelial goblet cellsreduce, submucosal lymphocytes, EOS infiltrating ease.2.Immunohistochemical results showed that:the p65of model mice,are mainlylocated in the cytoplasm of epithelial cells and glandular epithelial cells, rarenuclei, positive staining in the nuclei of stromal vascular endothelial cells and infiltrating inflammatory cells in the nasal mucosa, and mainly located in thebronchial epithelial cells, vascular endothelial cells, alveolar macrophages,alveolar epithelial cells and infiltrating inflammatory cells located in thebronchial epithelial cells, vascular endothelial cells, alveolar macrophages,alveolar epithelial cells and infiltrating inflammatory cells in lung tissue,anditsexpression was significantly higher than the control and hormone interventiongroup (P<0.05);the VCAM-1of model group, are positive for expression inthe cytoplasm of epithelial cells and vascular endothelial cells of nasal mucosa,bronchial epithelial cells were strongly positive expression, the numberof positive cells of alveolar macrophages, alveolar epithelial cells and lungmicrovascular endothelial cells increase, there are significant differences inthe three groups (P<0.05); the ICAM-1in the cytoplasm of model groupnasal epithelial cells, glandular epithelial cells, endothelial cells, bronchialepithelial cell, alveolar epithelial cells, pulmonary vascular endothelial cells,isstrong expression, also positive expression in nuclear,compared to the controlgroup and hormone group was significant difference (P<0.05); NF-κB p65innasal mucosa(r=0.791,0.802, P<0.05) and lung tissue (r=0.857,0.794, P<0.05)of model was significantly positively correlated to ICAM-1and VCAM-1.3. Western blot results show: The expression of NF-κB p65in the lung tissueof the model group is the significant higher than those in the control group andhormone interention group (P<0.05); VCAM-1in three groups is a significantdifference between three groups (P<0.05).4. ELISA result show: In AR mice, serum IL-4was significantly higher thanthe control group and intervention group hormone, and the differences weresignificant (P<0.05).5. Eosinophils (EOS) amount in BALF: the total number of cells in modelgroup were increased significantly in BALF, especially the amount of EOS,compared to the control group with hormone intervention group, thedifferences were significant (P<0.05).Conclusion:1. The consistency of NF-κB p65's expression in upper and lower respiratory tract allergy inflammation is confirmed that "the same airway, the samedisease" concept, allergic rhinitis is a risk factor of induce asthma.2. The activation of the NF-κB increase expression of ICAM-1and VCAM-1,which may relate to that the activation of vascular endothelial cells increasesecret ICAM-1, VCAM-1in the NF-κB regulation.3. Corticosteroids can inhibit nonspecific regulatory the activity of the NF-κBp65, downregulate ICAM-1and VCAM-1, play a role of anti-inflammatory,also confirms the therapeutic value of the hormones in allergic inflammation.