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Imiquimod Modulates Airway Remodeling In An Asthmatic Mouse Model

Posted on:2009-12-30Degree:MasterType:Thesis
Country:ChinaCandidate:J DaiFull Text:PDF
GTID:2144360245977878Subject:Respiratory medicine
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PartⅠAn asthmatic mouse model of airway remodelingObjective To build an asthmatic mouse model of airway remodeling.Methods Female mice were randomly divided into a control group,an asthmatic group and an imiquimod group,each in ten.Mice were sensitized on days 0 and 14 by OVA and challenged from days 24 to51 by OVA to establish a mouse model of chronic asthma characterized by airway remodeling.The imiquimod group was interfered with aerosol Imiquimod 30 min before challenge,The control group were treated with saline instead of OVA.Airway responsiveness was measured and changes in airway histology were observed.Results①Expiration resistance was determined before and after injection of acetylcholine chloride(5~405μg/kg),and expiration resistance of the asthmatic group was significantly elevated compared with that of the control group(P<0.05).②mucus hypersecretion,goblet cell hyperplasia,collagen deposition and the airway wall thickness(WAt/Pi), the bronchial smooth muscle thickness(WAm/Pi),the bronchial smooth nucleus counts(N/Pi)of asthmatic group were all significantly higher than those in control group(P<0.05).Conclusions An asthmatic mouse model of airway remodeling was successfully established and could be used in further study.PartⅡEffects of imiquimod on airway remodeling in an asthmatic mouse modelObjective To observe the effects of aerosol imiquimod on the airway remodeling and the expression of TGF-β1,Smads in an asthmatic mouse model.Methods The measurements included mucus secretion and the percent of goblet cell,collagen deposition around the bronchus by HE,AB-PAS and Masson's staining;WAt/Pi,WAm/Pi,N/Pi were measured by image analysis system;The protein expression of TGF-β1 in lung tissues was determined by immunohistochemical staining;The mRNA expressions of TGF-β1,Smad2 and Smad7 in the lungs were detected by RT-PCR.Results①mucus hypersecretion,goblet cell hyperplasia,collagen deposition and WAt/Pi,WArn/Pi,N/Pi of the asthmatic group were all significantly higher than those in control group(P<0.05),while decreased in the imiquimod group(P<0.05).②in the asthmatic group,the expression of TGF-β1 protein and mRNA,Smad2mRNA increased significantly when compared with control group(P<0.05),and decreased in imiquimod group(P<0.05).③the expression of Smad7mRNA in imiquimod group was significantly higher than that in asthmatic group(P<0.05).Conclusions The experimental data suggest that imiquimod aerosol inhalation could decrease the expression of TGF-β1 protein,TGF-β1 mRNA,Smad2mRNA,increase the expression of Smad7mRNA in a mouse model of chronic asthma and inhibit airway remodeling.
Keywords/Search Tags:Bronchial Asthma, Airway Hyperresponsiveness, Airway Remodeling, Acetylcholine chloride, Imiquimod, TGF-β1, Smads
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