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Experimental Study Of The Cellular And Molecular Biological Mechanisms Of Airway Inflammation In Asthma Treatment Method

Posted on:1998-07-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:X L CuiFull Text:PDF
GTID:1114360185969016Subject:Respiratory medicine
Abstract/Summary:PDF Full Text Request
Objective to elucidate the mechanism of anti-inflammatory effect of dexamethasone and methotrexate on pulmonary Th2 reaction and eosinophil infiltration in ovalbumin sensitized mice, and search for the possibility of aerosol administration of other anti-inflammatory drugs in the management of asthma except for glucocorticoids.Material and methods 60 C57b1/6 mice were sensitized and challenged with ovalbumin, aerosol dexamethasone and methotrexate were administered after challenge. Mice lung were fixed in paraformaldehyde and EL-4, EL-5 expression was detected by immunocytochemistry-in situ hybri-dization. Lung slides were also stained with eosin and hemotoxylin, patholo-gical changes were observed.Results Ovalbumin aerosol inhalation caused a mixed inflammatory infiltration dominated by CD4+ T lymphocytes and eosinophils in the lung of sensitized mice, 85.2-88.2% and 81.4-91.8% of the CD4+ T lymphocytes were IL-4 mRNA+ or IL-5 mRNA+ respectively, few CD8+ T lymphocytes were IL-4 or EL-5 positive, <2%. 78.8-80.8% of IL-4 mRNA+ cells and 78.0-86.8% of IL-5 mRNA+ cells were CD4+ T lymphocytes. Aerosol administration of dexamethasone and methotraxete after challenge inhibited EL-4 and IL-5 expression, and lung eosinophil infiltration was attenuated, dexamethasone was more effective. These two drugs had no effect on the ratio of IL-4 or IL-5 expression of CD4+ T lymphocytes, and the percentages of CD4+ T lymphocytes of the EL-4 mRNA+ or EL-5 mRNA+ cells were not affected,the anti-inflammatory effect was non-specific. In addition, aerosol administration of dexamethasone enhanced EL-4 expression and metho-traxete promoted eosinophil infiltration at 12 h after challenge.Conclusion and discussion Aerosol administration of dexamethasone and methotrexate attenuated pulmonary Th2 reaction in ovalbumin sensitized mice. It has been known that aerosol administration of drug exerts its effect at the site of inflammation,which is more effective and with less side effects,but at the beginning,aerosol administration might promote inflammation. In this way, oral or...
Keywords/Search Tags:Th2 reaction, Methotrexate, Immunocytochemistry-In situ hybridization, Th2 reaction, Immunocytochemistry, In situ hybridization
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