地塞米松对哮喘大鼠气道重建、肥大细胞及IL-10的影响

Effect of dexamethasone on airway remodeling and expression of mast and IL-10 in asthmatic rats

目的观察地塞米松对哮喘大鼠模型气道重建和肺组织肥大细胞、IL-10的影响,探讨地塞米松在气道炎症和气道重塑中的作用机制,为临床治疗提供依据。方法采用卵白蛋白(OVA)腹腔注射致敏和雾化吸入激发建立哮喘大鼠模型,30只SD大鼠随机分为3组,正常对照组(A)、哮喘组(B)、地塞米松干预组(C),每组10只。对肺组织切片行苏木精-伊红(HE)染色观察气道重塑情况。采用免疫组化和图像分析技术测定各组大鼠肺组织肥大细胞、IL-10的表达。结果哮喘组动物出现管壁增厚、平滑肌增生、黏液分泌增加等气道重塑的特征性改变,免疫组化染色显示气道各层细胞及炎性细胞均有IL-10表达减少。地塞米松干预组与哮喘组比较,炎症反应轻微,平滑肌增生、黏液分泌不明显,免疫组化染色显示各类细胞IL-10表达增高,与对照组比较差异有统计学意义。结论长期吸入变应原可导致气道重塑,肥大细胞、IL-10在气道重塑中发挥重要作用,地塞米松可通过抑制肥大细胞脱颗粒、增加IL-10表达发挥抑制炎症作用,进而缓解哮喘大鼠气道重塑的发生。

Objective To investigate the influence of dexamethasone on airway remodeling and lung mast cells,IL-10 in asthmatic rats. To discuss the mechanism of dexamethasone on airway inflammation and airway remodeling,to provide the experimental evidence for clinical treatments. Methods Rats were sensitized and challenged with ovalbumin（OVA） to establish the asthmatic model. Thirty SD rats were randomly divided into three groups：control group（A）,asthma group（B）,dexamethasone treatment group（C）,10 rats in each group. The changes of airway wall morphologic parameter were determined using a computer assisted image analysis system. The paraffin embedded sections of lung tissue underwent hemotoxylin and eosin（HE） staining and the lung pathological changes were observed.The expression of mast cells,IL-10 in lung tissues were detected by immunohistochemistry. Results After repeated allergen challenge,obvious infiltration of inflammatory cells and proliferation of goblet cells and smooth muscle were demonstrated in asthmatic rats. Expression levels of IL-10 in the epithelial cells of bronchi decreased obviously than in control animals. Compared with the asthmatic group,there was mild inflammation,smooth muscle hyperplasia,mucus secretion in dexamethasone group. Expression levels of IL-10 increased obviously,and there were significantly difference than that in asthmatic animals. ConclusionRepeated exposure of allergen induces airway inflammation and remodeling. Mast cell,IL-10 plays an important role in airway remodeling. Dexamethasone may restrain the increase of thickness of total airway wall and smooth muscle by inhibiting mast cell degranulation,increasing IL-10 expression in lung tissue.