Expression And Correlation Studies Of Nuclear Factor-κB P65, HIF-1α And VEGF In The Nasal Mucosa Of Allergic Rhinitis Mice

Objective: Allergic rhinitis (allergic rhinitis, AR), which is start with therelease of transmittera mediated by IgE after the specific individual exposed toallergens, is a chronic inflammation of the nasal disease involved of a varietyof immune cells and cytokines. In recent years, the incidence was in a largeascending trend. It had an influence up on approximately10%to25%ofglobal population, especially in the industrially developed countries, whichhave a higher prevalence. Therefore, the issue of searching for the effectivetreatment of AR has received extensive attention.As tissue anatomical similarities of the upper and lower respiratory,inflammatory lesions rarely confined to one area. Epidemiological data shows,more than30%of the patients with allergic rhinitis have a tendency to developinto asthma,50%of asthma patients are company with allergic rhinitis. In2001, the World Health Organization clearly proposed a new ideas that allergicrhinitis and asthma is "one airway-one disease ".Therefore, the correlationalresearch between the upper and lower respiratory tract inflammation becomecurrent research focus.Recent studies have found that transcription factors play an importantrole in regulation of inflammation. Some transcription factors involved in theprocess of allergic and play a role in inflammation enlarge by regulatingcascade waterfall effect between the inflammation-related factors andinflammatory mediators, and then play a pivotal role in the inflammation andimmune responses. In respiratory allergic diseases, more research abouttranscription factor is nuclear factor-κB p65and HIF-1α.This artical aims to investigate the correlation between allergic rhinitisand bronchial asthma from macro and micro aspects, we also investigate the expression of Nuclear factor-κB p65, HIF-1α and VEGF in the upper andlower airway in mice with allergic rhinitis, so as to understand the role of themin the pathogenesis of allergic rhinitis. The research results may bring newinspiration for the treatment of the upper and lower airway inflammatorydisease and provide a new theoretical basis for the study of new treatmentstrategies of allergic rhinitis.Methods:30FVB mice were randomly divided into control group,allergic rhinitis group(AR group) and hormone intervention group, AR groupconducted the basal sensitization with intraperitoneal injection of10%eggalbumin (ovalbumin,OVA), and then exposed to6%OVA suspensionintranasally, so as to induce mouse model of allergic rhinitis. Saline was usedin Control group instead of OVA, Hormone intervention group conductedintraperitoneal injection of dexamethasone before local excitation. The micewere killed24h after the last challenge, then took the heart blood, using forsurvey the level of IL-4with ELISA. Preparing the bronchoalveolar lavagefluid (bronchoalveolar lavage fluid,BALF), which was count for inflammatorycell.20mg lung tissue specimen was homogenized to determine the proteincontent of nuclear factor-κB p65, HIF-1α and VEGF. The remaining left lungand nasal tissue were fixed, embedded with parafin and pathological sectionwas made, then stained with hematoxlin-eosin for histological analys andimmunohistochemical staining for the expression of protein. Multi-factoranalysis of variance analysis was used to process the data, regard α=0.05asthe level of significance difference.Results：1Model assessmentAR models were successfully established in10animals, which hadtypical nasal symptoms, and all of their behavioral stack scores were morethan5points; Compared with AR group,symptoms of Hormone interventiongroup were significantly relieved, stack scores were less than5points; controlgroup almost had no nasal symptoms of allergic rhinitis.2Organization morphology change 2.1The performance Nasal mucous membrane: The nasal mucosa ofcontrol group has no obvious inflammatory changes. Nasal mucosa of ARgroup showed off a large number loss of cilia structure, varying degrees ofedema, proliferation of small blood vessels, and infiltrations of inflammatorycells such as eosinophils, mononuclear cells and lymphocytes. Nasalinflammation in hormone intervention group were significantly reducedcompared with the AR group.2.2The performance of lung tissue: Bronchi and blood vessels has noinflammatory cell infiltration in the control group. Bronchiolar smooth muscledoes not appear proliferation. Epithelial cell loss were observed in AR group,the form of bronchial wall was irregular, bronchiole smooth muscle appearedslight proliferation, more inflammatory cell infiltration can be seen inbronchial wall and the vessel wall. The pathological changes of lung tissue inintervene group were significantly alleviated, but the changes(such asinflammatory cells infiltration) did not completely disappear.3Serum levels of IL-4in miceIn AR mice, IL-4in serum was significantly higher than the controlgroup and intervention group hormone, and the differences were significant(P<0.05). Compared the hormone intervention group with control group, thedifference was not statistically significant(P>0.05).4Eosinophils (EOS) amount in bronchoalveolar lavage fluid (BALF)In AR model group, the total number of inflammatory cells wereincreased significantly in BALF, especially the amount of EOS. Comparedwith the AR group,the total number of inflammatory cells and EOS in BALFin the hormone intervention group and control group were significantlyreduced, the differences were significant (P<0.05). Compared the hormoneintervention group with control group, the difference was not statisticallysignificant(P>0.05).5The expression of p65,HIF-1α and VEGF in mice were consistent in theupper and lower airwaysCompare with the control group and intervention group, the expression of p65, HIF-1α and VEGF were significantly increased in AR group, and thedifferences were significant (P<0.05). There was positive correlation betweenHIF-1αand NF-κB in nasal mucosa of AR group (P<0.05),here was alsopositive correlation between HIF-1αand VEGF in nasal mucosa of AR group(P<0.05).Conclusion:Allergic rhinitis could cause inflammation of bronchial lung tissue,allergic inflammation between the upper and lower respiratory tract wasclosely related.We speculated that under the stimulation such as inflammation and lowoxygen, p65regulated the expression of the HIF-1α, which promoted theexpression of VEGF in mass, then made allergic airway inflammationoccurred.For the treatment of allergic rhinitis, we might seek a new breakthroughin the level of transcription factor. NF-κB p65and HIF-1α may become anew kind of therapic place and targets in immune regulation, especially thegene drugs which can directly suppress the activity of NF-kappa B or HIF-1α might become the research focus in recent years.