The Role Of HMGB1/TLR4/NF-kB Signaling Pathway In The Pathogenesis Of Allergic Rhinitis In Rats And The Effect Of Glucocorticoids

Background:The global prevalence rate of allergic rhinitis(AR)is about 10%-40%,with a population of more than 500 million,and about 25% of AR patients are often accompanied by asthma.The prevalence rate of AR in China is about 4%-38%,and the differences are related to the environment and economic level of different regions.AR symptoms severely interfere with sleep,leading to daytime sleepiness and poor quality of life.In the survey of patients with moderate and severe AR,compared with those with mild AR,anxiety,depression,fatigue,social disturbance and cognitive dysfunction were significantly increased in patients with moderate and severe AR.Sleep disorders extend to parents of children with AR,with 75 percent of parents reporting poor sleep quality.The pathogenesis of AR is a complex network structure,and the pathogenesis is complex,involving a variety of immune cells,inflammatory mediators and signaling pathways.More and more evidences show that the HMGB1/TLR4/NF-k B signaling pathway is involved in the pathogenesis of allergic rhinitis.This study aims to provide a new target for the treatment of AR.To provide theoretical support for the research and development of new drugs to treat AR diseases.Objective: To study the role of HMGB1/TLR4/NF-KB signaling pathway in rats with allergic rhinitis,and the effects of local and systemic application of glucocorticoids on HMGB1/TLR4/NF-KB signaling pathway and inflammatory factors.Methods:Forty male Wister rats were numbered according to their body weight and randomly divided into 4 groups(10 rats in each group)by random number table:group A was the normal control group,group B was the sensitized group,group C was the triamentonide group,and group D was the dexamethasone group.The behavioral changes of rats were observed.The pathological changes of nasal mucosa were observed by HE staining.The contents of IL-4,IL-10,INF-γ,IL-17 A and TGF-β1 in serum of each group were detected by ELISA,the contents of HMGB1 in nasal mucosa tissue homogenate of each group were detected by Western blot,and the contents of TLR4 and NF-k B in nasal mucosa tissue homogenate of each group were measured by real-time fluorescence quantitative PCR.Result:AR model rats showed severe nasal scratching,sneezing and runny nose,and severe infiltration of inflammatory cells in nasal mucosa tissue.(1)Compared with group A,the contents of IL-4 and IL-17 A in group B were significantly increased(P < 0.05 for all),while TGF-β1 and INF-γ were significantly decreased(P < 0.05 for all).Compared with group B,the proportions of IL-4,IL-17 A,and TGF-β1 and INF-γ in groups C and D were decreased to varying degrees(all P <0.05),and the proportions of TGF-β1 and INF-γ were increased to varying degrees(all P < 0.05).There were no significant differences in the proportions of IL-4,IL-17 A,TGF-β1 and INF-γ between group C and group D(all P values were > 0.05).(2)Compared with group A,the protein expression levels of HMGB1,TLR4 and NF-k B in nasal mucosa of groups B,C and D were significantly increased,with statistical significance(all P < 0.05).Compared with group B,the protein expression levels of HMGB1,TLR4 and NF-k B in groups C and D were decreased to varying degrees,with statistical significance(P < 0.05).There were no significant differences in HMGB1,TLR4 and NF-k B protein expression between C and D groups(P≥0.05).(3)Pearson correlation analysis of HMGB1,TLR4 and NF-k B protein correlation showed significant positive correlation(P < 0.001).Conclusion:The HMGB1/TLR4/NF-k B signaling pathway is involved in the pathogenesis of allergic rhinitis in rats.Local and systemic application of glucocorticoids can significantly reduce the symptoms of allergic rhinitis in rats by inhibiting the HMGB1/TLR4/NF-k B signaling pathway,thereby down-regulating the expressions of pro-inflammatory factors IL-4 and IL-17 A,and simultaneously up-regulating the expressions of anti-inflammatory factors TGF-β 1 and INF-γ.Local or systemic application of glucocorticoids can play a therapeutic role in the treatment of allergic rhinitis in rats through the HMGB1/TLR4 / NF-k B signaling pathway.