The Expression Of BMP-8 And Effects Of Intranasal Budesonide On The Remodeling Of Nasal Mucosa In A Murine Model Of Allergic Rhinitis

Objective: We observed the pathological changes of nasal mucosa after different doses of budesonide,and measured the content of bone morphogenetic protein-8(BMP-8a and BMP-8b),OVA-sIgE and nasal lavage in serum and IL-4 and IL-13 in nasal lavage fluid to investigate the expression of bone morphogenetic protein-8 and the inhibitory effect of budesonide on nasal mucosal remodeling in murine model of allergic rhinitis.Methords:Forty female BALB/c mice were randomly and equally divided into four groups,group A,group B,group C,and group D.25 ug of ovalbumin(OVA)and 2 ml of aluminum hydroxide was dissolved in 50 uL of normal saline,which was applied to mice in group B,C,and D.Mice in group A were treated with the same amount of normal saline(NS).On days 0,7,and 14,four groups of mice were intraperitoneally injected with the corresponding reagents.From day 22 to day 28,mice in groups B,C,and D were given 10 uL of ovalbumin intranasally on both side of the nasal cavity.The mice in group A were treated with normal saline in the same way.After the last nasal challenge at the end of week 4,we observed the nasal symptoms of each mouse within 30 minutes and record the number of nasal scratching and sneezing.The mice in each group were stimulated with normal saline and ovalbumin twice a week from week 5 to week 16 sequentially.The mice in group C and D were given budesonide at a dose of 3ug/20 g and15ug/20 g respectively in the meantime on both side of the nasal cavity once a day.After the last nasal stimulation at the end of the week 16,nasal symptoms were observed and recorded including the number of nasal scratching and sneezing in the 4 groups of mice within 15 minutes.Then,the mice were anesthetized and sacrificed to preserving serum and nasal lavage and nasal tissue.The nasal mucosa was stained with Masson's Trichrome,hematoxylin-eosin,toluidine blue and periodic acid-Schiff to observed the pathological changes.ELISA was used to measure the content of IL-4,IL-13 in nasal lavage fluid and BMP-8a,BMP-8b,OVA-sIgE in serum.SPSS 24.0 was used for statistical analysis.The data of each group were analyzed using the nonparametric Kruskal-Wallis test.Pairwise comparisons were conducted using a Mann-Whitney U-test and corrected with Bonferroni when the difference was statistically significant.Results:(1)The concentration of IL-4 and IL-13 in nasal lavage fluid and BMP-8a,BMP-8b and OVA-sIgE in serum of each group: There was no significant difference in the content of BMP-8a in four groups.The concentration of BMP-8b in group B was the most significantly increased,following successively by group C,group D and group A.The comparison among four groups was statistically significant,P<0.05.The changes of IL-4,IL-13 and OVA-sIgE concentrations were the same with BMP-8b.Histological changes of nasal mucosa in each group: the sequence of thickness of the subcutaneous layer was group B,group C,group D and group A,the difference was statistically significant among four groups(P<0.05).The number of goblet cells in each group were showed changed in sequence: group B has the highest content,group C takes the second place and group D was less than group C,group A had the lowest concentration,and the difference of airwise comparisons was statistically significant(P<0.05).The number of mast cells were the highest in group B and the lowest in group A,group C and group D fell in between,the difference between group C and group D has not statistically significance.The gland diameter in group B was significantly higher than the C group and the D group,and the pairwise comparison among this three groups was significant,but there was no difference between group D and group A.Conclusion:Nasal mucosa remodeling could occur after long-term and continuous ovalbumin stimulation.Different doses of budesonide has different inhibitory effects on nasal mucosal remodeling,the higher doses have a better inhibitory effect.BMP-8b overexpresses in allergic rhinitis mice and is positively correlated with severity of allergic rhinitis.There was no significant difference in the expression of BMP-8a whether the severity of allergic rhinitis.