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The Experimental Research Of The Intranasal Corticosteroids' Influence On Nasal Mucosa Pathologic Change In Allergic Rhinitis

Posted on:2009-03-04Degree:MasterType:Thesis
Country:ChinaCandidate:B B XieFull Text:PDF
GTID:2144360245989851Subject:Otolaryngology
Abstract/Summary:PDF Full Text Request
Objective: To investigate the influence of the inhaled corticosteroids to the remodeling of the nasal mucosa in the allergic rhinitis, by establishing the allergic rhinitis model of the rats, which induced by OVA.Methods: 300 Sprague-Dawley(SD) rats are selected and randomly divided into two groups: the normal Group A used for control and the experimental group. The number of the rats in Group A is 60 and the experiment group is 240.First of all, make the rats in experimental group be allergic with ovalbumin(OVA) and enhance it and do local stimulation in order to establish the animal model of allergic rhinitis. While do intra-peritoneal injection with physiological saline in the same volume as that of ovalbumin(OVA) in the experimental group and intranasal dropping on the rats in normal Group A. Next, the rats in experimental group are randomly divided into four groups, i.e. Group B, Group C, Group D, Group E. The number of rats in each group is 60.Randomly select 10 rats to kill from each groups respectively at the end of the first, second, fourth, eighth, twelfth and sixteenth week after treatment. Randomly select one from that ten rats in each group for micro-vascular casting of nasal mucosa, and the remaining nine are to get pathological examination, PCR and transmission electron microscope in order that I can observe the morphological changes, the micro-vascular casts and the expression of TGF-β1,FGF-2 in the nasal mucosa. And then, the rats in Group A get the intranasal dropping with physiologic saline in the same volume twice a week; rats in Group B are under no stimulation or treatment; rats in the Group C are no longer stimulated with OVA, but they are going to have fluticasone propionate(FP) nasal spray, each side 50μl /per day; rats in Group D still get the intranasal dropping on each side with OVA in the same volume and concentration twice a week; rats in Group E also get the intranasal dropping on each side with OVA in the same volume and concentration twice a week, moreover, they get FP nasal spray, each side 50μl /per day.Results: The model on the rats in experimental group is established successfully: all the rats in the experimental groups show obvious symptoms: grasping noses, sneezing and running nose. After allergen stimulation, the nasal mucosa showed remodeling changes such as epithelial denudation, but it does not occur to the bottom and inflammatory cells infiltration becomes obvious with the help of optical microscope. And there are metaplasia of the goblet cells in epithelia and the number of gland and blood vessels increase in the mucosal layer and glandular vessels become thick. Cilia of epithelial shed to different extent and are uneven under the electron microscope, and the layers of reticular formation of basal membrane become thick, and collagen deposition and fabric hyperplasia are seen. There is inflammatory cells infiltration of different degrees around the blood vessels and edema in cells. Edemas in tissue spaces are also obvious and the structures between cells are not destroyed. And the micro-vascular in mucosa increase apparently. They are tortuous, branching, thick and thin. Density of blood capillary is increased and blood capillary becomes netted. The positive expression of immunohistochemistry of TGF-β1, FGF-2 rise obviously, in the meantime, TGF-β1 mRNA expression rises as well. Because of avoiding the exposure of allergen, epithelial denudations of mucosa in Group B are reducing from the eighth week. Till the sixteenth week, epithelial damage of the mucosa and inflammatory cells infiltration reduced obviously. TGF-β1,FGF-2 positive expression of immunity and TGF-β1m RNA expression drop in the eighth week. Under the treatment with corticosteroids, the degree of epithelial denudations and inflammatory cells infiltration of the rats in Group C are reduced, and micro-vascular are lessened in the eighth week. In the sixteenth week, epithelia of nasal mucosa are basically complete, glandular metaplasia alleviates, inflammatory cells infiltration become unobvious. The positive expression of immunohistochemistry of TGF-β1, FGF-2 and TGF-β1 mRNA expression decline in the fourth week, however, in the sixteenth week they draw close to the normal groups'. The positive expression of immunohistochemistry of TGF-β1, FGF-2 and TGF-β1 mRNA expression last high in Group D due to the continuously contact with allergen and enhancing remodeling. There are no obvious changes in morphology of the rats in Group E. Even in the sixteenth week, metaplasias of the goblet cells in epithelia are clear to be seen. Besides, a lot of mucus deposits in goblet cell, micro-vascular under the mucosa become thick. The positive expression of immunohistochemistry of TGF-β1, FGF-2 and TGF-β1 mRNA expression decline in the eighth week. Compared with Group C there is no differences in statistics in the sixteenth week.Conclusion: 1. The animal model of the allergic rhinitis can be established on the SD rats using the ovalbumin as the allergen. 2. The remodeling of the nasal mucosa can be found in allergic rhinitis. If allergen can be avoided, the symptoms can be alleviated and the remodeling will reduce by itself; if the allergen are continuously contacted, the remodeling will aggravate. 3. Corticosteroids can control the symptoms of the allergic rhinitis better and reverse the remodeling to some extent and perform the therapeutical effects. While if allergen can not be avoided, although the symptoms can be controlled with corticosteroids somehow, it is impossible to reverse the remodeling completely in a short time. And it cannot retro-converse or repair the nasal mucosa while the irreversibile change has occurred. 4. Growth factors such as TGF-β1, FGF-2 express obviously in the mucosa in allergic rhinitis, and the expression could be lowed down by corticosteroids, maybe that's one of the mechanisms of the corticosteroids to cure the AR. 5. Avoid allergen is still the preferred approach for the treatment of the allergic rhinitis. If we can make sure to avoid allergen, the therapy supplemented by corticosteroid is one of good choice.
Keywords/Search Tags:Allergic rhinitis, nasal mucosal remodeling, corticosteroids, growth factors
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