气道炎症和重构在小鼠哮喘模型中的变化及地塞米松的干预作用

Airway inflammation and remodeling in murine model of chronic asthma and the effects of dexamethasone

目的 观察小鼠慢性哮喘模型中气道炎症和重构的变化及地塞米松的影响。方法77只BALB/c小鼠随机分为对照组、哮喘组、哮喘 +激素组 ,卵蛋白致敏并反复雾化吸入 2、4及 8周 ,造成慢性哮喘模型 ,哮喘 +激素组腹腔注射地塞米松。借助MetaMorph图像分析软件测量单位气道面积炎性细胞数目、基底膜周径 (Pbm)、上皮黏膜层面积 (WAmuc)、平滑肌面积 (WAm)、气管内壁面积 (WAi)、胶原面积 (Wcol)、杯状细胞的比例和气管基底膜 (/ 1mm)上BrdU+ 细胞数目。结果哮喘组和哮喘 +激素组单位气道面积炎性细胞计数高于对照组 ,且哮喘组高于哮喘 +激素组 ;雾化吸入OVA 2、4及 8周组炎性细胞计数无显著差异。哮喘组WAmuc/Pbm、WAm/Pbm及WAi/Pbm较对照组和哮喘 +激素组明显增加 ,哮喘 +激素组高于对照组。各组在雾化吸入 2、4及 8周后WAmuc/Pbm、WAm/Pbm、WAi/Pbm无显著性差异。哮喘组和哮喘 +激素组Wcol/Pbm大于对照组 ,哮喘组大于哮喘 +激素组。在哮喘组 ,雾化 8周后Wcol/Pbm大于雾化 2周后。对照组杯状细胞积分为 0分 ,哮喘组杯状细胞积分高于哮喘 +激素组。在哮喘 +激素组 ,雾化吸入 4及 8周后杯状细胞积分低于雾化吸入 2周后。哮喘组和哮喘 +激素组气管基底膜上BrdU+ 细胞数目明显高于对照组 ,哮喘组高于哮喘 +激素组?

Objective To observe the changes of airway inflammation and remodeling in a murine model of chronic asthma and the effects of dexamethasone (DXM).Methods 77 BALB/c mice were randomly divided into three groups:control group,asthma group and DXM treated group.The asthma group and DXM treated group were sensitized and repeatedly challenged with ovalbumin (OVA) for 2,4 and 8 week,respectively.The morphological parameters including the number of inflammatory cell per unit airway,bronchial basement membrane perimeter (Pbm),area of the mucous cell layer (WAmuc),smooth muscle area (WAm),inner way area (WAi)),collagen area (Wcol),goblet cell percentage and BrdU-positive cell per mm Pbm were measured by MetaMorph image analysis software.Results Inflammatory cells increased both in asthma group and in DXM treated group but the increment was more significant in asthma group than that in DXM treated group.However,the differences of numbers of inflammatory cells in the models with 2,4 and 8 weeks' OVA exposure were not statistically significant.WAmuc/Pbm,WAm/Pbm and WAi/Pbm in asthma group were significantly greater than those in DXM treated group and control group while those in DXM treated group were still greater than those in control group after OVA exposure for 4 and 8 weeks.The differences of WAmuc/Pbm,WAm/Pbm and WAi/Pbm in three groups with OVA exposure for 2,4 and 8 weeks were not statistically significant.Wcol/Pbm was increase in the asthma group and DXM treated group compared to that in control group while in asthma group the increment was significant than that in DXM treated group.Morever,Wcol/Pbm elevated in asthmatic group from 2 weeks to 8 weeks significantly.Goblet cell score was zero in control group and increased in asthma group and DXM treated group although it was more significant in asthma group.However,the scores were lower in DXM treated group after 4 and 8 weeks than that after 2 weeks.The number of BrdU-positive cell per mm Pbm increased in asthma group and DXM treated group compared to that in control group while in asthma group it was larger than that in DXM treated group.The number of BrdU-positive cell in asthmat and DXM treated groups groups increased from 2 weeks to 4 and 8 weeks.Conclusions Airway inflammation and remodeling occurrs in the early phase of asthma.However,no evidence supports a progressive exacerbation of inflammation and remodeling along with asthma process.Early intervention with steriod might inhibit airway inflammation and epithelial hyperplasia which could not prevent but partially inhibit airway remodeling.