基于外泌体蛋白组学探讨辅舒良治疗大鼠变应性鼻炎的作用机制OA

Objective To study the mechanism of Fluticasone Propionate Nasal Spray in the treatment of allergic rhinitis in rats using exosomal proteomics.Methods SD rats were randomly divided into blank group,model group and nasal spray hormone group(treat-ment group),with 10 rats in each group.Except for blank group,all the rats in the other group were injected intraperitoneally with 1 mL of the mixture containing 0.3 mg OVA and 30 mg Al(OH)3,sensitized once every other day,and then systemically sensitized for seven consecutive times,and the rats were given 0.05 mL of 5％OVA by nasal drops on each side once daily for seven consecutive times for nasal sensitization.From day 22,the rats in treatment group were intervened with cochlearine nasal drops once a day for 21 consecutive days.Blood from the abdominal aorta and nasal mucosa tissue were taken from the rats at day 3 after the end of all interven-tions.The histopathological changes of nasal mucosa were observed by HE staining,and the levels of IL-4 and IFN-γ in nasal mucosa were detected by immunohistochemistry.Exosomes were extracted from rat peripheral blood plasma by ultracentrifugation,and the morphology of exosomes was detected by transmission electron microscopy and particle size analysis(NTA).Significantly differentially expressed proteins in rat plasma exosomes were screened according to the criteria of P＜0.05 and|log2(Fold Change)|＞1.5,and then were subjected to GO,KEGG enrichment analysis and PPI analysis.Results Compared with model group,nasal mucosal edema and inflammatory cell infiltration were reduced,nasal mucosal IL-4 expression was decreased(P＜0.05),and nasal mucosal IFN-γ ex-pression was increased in treatment group(P＜0.05).Proteomics showed that relative to blank group,there were 92 differential proteins in model group,including 41 upregulated proteins and 51 downregulated proteins;relative to model group,there were 475 differential proteins in treatment group,including 325 upregulated proteins and 150 downregulated proteins.GO enrichment revealed that the dif-ferentially expressed proteins between model group and treatment group were involved in biological processes,molecular functions,and cellular components,and they were mainly enriched in protein activation cascade response,serine-type endopeptidase inhibitor activity,and extracellular gaps.KEGG analysis showed that the differential proteins between model group and treatment group were in-volved in multiple signaling pathways,with the highest involvement of differential proteins in the complement and coagulation cascade signaling pathway.PPI analysis of differential proteins between model group and treatment group revealed that six differential proteins,including F2,Plg,Alb,Serpinc1,Serping1 and Fga,were located in the center of the functional network,and most of the proteins belonged to complement and coagulation cascade signaling pathway.The differential proteins were associated with the complement and coagulation pathways were exosomes C4b and C1qc after simultaneously compared between blank group and model group,and be-tween model group and treatment group.Conclusion Fluticasone Propionate Nasal Spray may improve the inflammatory response in allergic rhinitis in rats by modulating exosomal proteins C4b and C1qc,altering the components of coagulation and fibrinolytic sys-tems,and affecting the complement and coagulation cascade signaling pathway.