目的 观察布地奈德雾化吸入对哮喘小鼠糖皮质激素受体(GR)和核因子-κB(NF-κB)表达的影响.方法 24 只健康6~8 周龄雄性BALB/c 小鼠随机分为生理盐水对照组、哮喘模型组(哮喘组)和布地奈德治疗组(BUD 组),每组8 只.通过腹腔注射卵清蛋白和氢氧化铝混悬液致敏以及卵清蛋白溶液雾化吸入激发哮喘.末次激发24 h 后处死小鼠,取支气管肺泡灌洗液(BALF)进行嗜酸性粒细胞计数,取肺组织行病理学检查及免疫组化检测GR 和NF-κB 表达水平.结果 哮喘组BALF 中嗜酸性粒细胞计数较对照组显著增加(P<0.05);BUD 组与哮喘组相比嗜酸性粒细胞数量显著减少,但仍较对照组增高(P<0.05).哮喘组小鼠肺组织可见嗜酸性粒细胞、淋巴细胞等炎症细胞浸润,BUD 组炎症细胞浸润较哮喘组明显减轻.哮喘组GR 阳性细胞百分比与对照组比较明显减少(P<0.05),BUD 组GR 阳性细胞百分比较哮喘组明显增加,但仍低于对照组(P<0.05);哮喘组NF-κB 阳性细胞百分比较对照组明显增加(P<0.05),BUD 组NF-κB 阳性细胞百分比较哮喘组明显减少,但仍高于对照组(P<0.05).结论 BUD 治疗哮喘小鼠的作用机制可能与上调GR 水平及抑制NF-κB 的活性有关.

Objective To study the effect of budesonide aerosol inhalation on the expression of glucocorticoid receptor (GR) and nuclear factor (NF)-κB in asthmatic mice. Methods Twenty-four healthy male BALB/c mice aged 6 to 8 weeks were randomly divided into three groups (n=8 each): normal saline (control group), asthma model (asthma group) and budesonide-treated asthma (BUD group). Asthma was induced by intraperitoneal injection of ovalbumin (OVA) and aluminium hydroxide suspension and aerosol inhalation of OVA solution. Mice were sacrificed 24 hours after the last challenge. Eosinophil count in the bronchoalveolar lavage fluid (BALF) was determined. Pathological examination of the lung tissues was performed and the expression levels of GR and NF-κB were measured by immunohistochemical analysis. Results Eosinophil count in the BALF was significantly higher in the asthma and BUD groups than in the control group (P<0.05). BUD treatment decreased eosinophil count in the BALF compared with the asthma group (P<0.05). The lung tissues in the BUD group showed a less severe infiltration of eosinophils and lymphocytes compared with the asthma group. The percentage of GR-positive cells in the asthma group decreased significantly compared with the control group (P<0.05), and the percentage of GR-positive cells in the BUD group increased significantly compared with the asthma group (P<0.05). Compared with the control group, the percentage of NF-κB-positive cells increased significantly in the asthma group (P<0.05), and the percentage of NF-κB positive cells in the BUD group was significantly reduced compared with the asthma group (P<0.05). Conclusions The action mechanism of budesonide in treating asthmatic mice may be related to the upregulation of GR expression and the inhibition of NF-κB activity