| In 1992, Bousquet advocated that chronic allergic inflammatorycondition may results in airway structural changes in asthma, andtermed it "airway remodeling". It took several years to begin tounderstand what the term airway remodeling meant. In asthma, theairway remodeling include epithelial shedding, thickening of thebasement membrane (lamina reticularis), an increase in blood vesselcross-sectional area, airway smooth-muscle hyperplasia andhypertrophy, mucous gland and goblet cell hyperplasia, andincreased collagen deposition.The upper and lower airways show similar nucosal structure andinflammatory reactions to irritants and allergens. Increasing evidenceshowed that there is no difference between nasal mucosa andbronchial line in cell infiltration and expression of cytokines inallergic inflammatory condition. However, in allergic rhinitis, thestructural changes of nasal mucosa remain to be fully investigated,and there is a debate on whether the nasal mucosal remodeling isexists in the disease.In the present study, by using a prolonged OVA exposuredmurine model, we found some characters of remodeling in nasalmucosa of allergic rhinitis. Then as the remodeling is considered tobe the results of allergic inflammation and anti-inflammatorytreatment could inhibit the remodeling processes in asthma weredemonstrated in a few studies, We wonder if these changes would beinhibited by anti-allergic inflammatory treatment in nasal allergy.Glucocorticoid and CysLT1 receptor antagonists is both effectiveanti-allergic inflammatory agent in airway allergic inflammatorydisease, and are both widely used in the treatment of allergic rhinitis.We hypothesize that treatment with glucocorticoid and CysLT1receptor antagonists could inhibit the remodeling changes in nasalallergic inflammation.Part 1 Remodeling in a guinea pig model of allergic rhinitis.24 male Hartley guinea pigs, (4 weeks male 250-300g) wererandomly divided into four groups (group 1 -4). Animals weresensitized to intraperitoneal (i.p.) ovalbumin (OVA) with an injectionof a 1ml suspension of OVA and aluminum hydroxide (Al(OH)3 )in 0.9% saline on day 1. And On day 7, a 1ml suspension of OVAand AL(OH)3 in 0.9% saline were injected i.p. as a booster. Controlanimals (group 1) were given saline only. Sensitized guinea pigswere subjected to either brief or prolonged exposure to allergen.Both of the brief exposure group (group2) and prolonged exposuregroup (group3 and 4) received a daily intranasal challenge with 5%OVA in 0.9% saline from Day 21 to Day 27, the prolonged exposuregroup (group 3 and 4) followed by twice weekly exposure to 5%OVA in 0.9% saline intranasal for an additional 7 and 11 weeksrespectively. Control group (group 1) were given intranasal 0.9%saline only daily one week and a further twice weekly for 11 weeks.At 24 h after the last intranasal challenge, guinea pigs were killedwith an intraperitoneal overdose of sodium pentobarbital. The headof each animal was removed and fixed in 10% neutral bufferedformalin for 24 hours, then decalcified in 5% trichloroacetic acid for10 days. The nasal cavity was transversely sectioned at the level ofthe incisive papilla of the hard palate. The tissue block wasembedded in paraffin.Paraffin sections 3 μm thick were stained with hematoxylin andeosin (H&E) stain for determin eosinophilial infiltration andepithelial damage, alcian blue (pH, 2.6)-periodic acid-Schiff(AB-PAS) stain for determin goblet cell hyperplasia and Masson'sTrichrome(MT) stain for determin extracellular matrix depositionThe number of eosinophils and gland cells in nasal septum,AB-PAS-positive cells in the surface epithelium in nasal septalmucosa were counted. The percentage area of MT stainedextracellular matrix in septal mucosa and conchae and damage ofepithelium were determined by an image analyzer.Significant eosinophil infiltration was observed in thesensitized groups (group2,3 and 4). The Control group (group1) onlypresented a few eosinophils.In 1 week exposure group (group2),there is no significant epithelial damage was observed, a significantepithelial damage including cilia absent and upper layer erosion wasobserved in 8 and 12 weeks exposure groups (group3 and 4).Anincrease in AB-PAS-positive cells was observed in the mucosa ofnasal septum in the prolonged allergen exposure groups (group3 and4) but not in the brief allergic inflammation group(group2)comparison with the control (group1).In the control group (group 1), there was little collagen stainingbeneath the basement membrane of epithelial and around the glandsand vasculature. The brief OVA exposure group (group 2) have notshowed an increasing of collagen fibrils within the mucosa of nasalseptum and conchae. In contrast, after prolonged OVA exposure(group 3,4) an increase in matrix was observed. Furthermore in boththe nasal septum and conchae, we found a significant increasing ofECM deposition in a further prolonged exposure for 12 weeks(group4) compare to 8 weeks (group3).Part 2 remodeling of nasal mucosa in nasal allergy wassuppressed by Dexamethasone and Pranlukast.In this part we employeed a guinea pig model as the previouspart.we administrated dexamethasone and pranlukast in group 3 andgroup 4, while the group 1 as a negatve control and group 2 aspositive control. As the results,Significant eosinophil infiltration,epithelial damage, goblet hyperplasia and extracellular matrixdeposition was observed in the ovalbumin sensitized group(OSG)but not in the OVA+dexamethasone group(ODG) andOVA+pranlukast group(OPG).ConclusionIn summary, the study presented here has shown that prolongedallergen exposure of sensitized guinea pigs results in persistentremodeling of the nasal mucosa. Epithelial damage, goblet cellhyperplasia and extracellular matrix deposition were observed as thefeatures of remodeling of allergic rhinitis. And these changes aresignificant inhibited by injection of dexamethasone and pranlukastintraperitoneal. The results indicats the importance of earlyintervention with glucocorioids and cysLT1 receptor antagonists inallergic rhinitis.
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