【作者】 周林福； 殷凯生； 朱自路； 姚欣； 解卫平； 朱毅； 毛辉； 吴剑卿；

【机构】 南京医科大学第一附属医院呼吸内科； 南京医科大学生化与分子生物学系；

【摘要】 目的:哮喘系多基因参与的具有遗传易感性的慢性气道炎症性疾病,其中嗜酸细胞（EOS）浸润是最为显著的病理特征。研究三氧化二砷（As₂O₃）对哮喘小鼠肺组织核因子κB（NF-κB）激活及其抑制蛋白IκBα表达的影响作用,进一步探讨As₂O₃抗炎作用的可能机制。方法:BALB/c小鼠36只随机分为对照组6只、哮喘组24只（分为卵蛋白末次激发后1h,4h、12h和24h时间点各6只）和As₂O₃治疗组（4mg/kg）6只。采用Diff-Quick染色、电泳迁移率实验（EMSA）和免疫印迹实验（Western blot）分别检测支气管肺泡灌洗液（BALF）中EOS募集、肺组织NF-κB活性和IκBα表达水平。结果:对照组BALF中EOS募集、肺组织NF-κB活性和IrBα表达分别为（0.56±0.22）%、51.47±4.53和0.80±0.25;与对照组比较,哮喘组BALF中EOS募集和肺组织NF-κB活性显著增加（P均<0.01）,而肺组织IκBα表达显著减少（P<0.01）,其中NF-κB活性于1h显著增加（P<0.01）、4h达到峰值（P<0.01）而12h（P<0.01）至24h（P<0.05）显著减少;与哮喘组比较,治疗组BALF中EOS募集和肺组织NF-κB活性显著减少（P均<0.01）,而肺组织IκBα表达显著增加（P<0.01）,并且BALF中EOS募集与肺组织IκBα表达、肺组织NF-κB活性与肺组织IκBα表达之间均呈显著性负相关（r=-0.82和-0.94,P<0.01）。结论:肺组织NF-κB过度激活可能是哮喘慢性气道炎症持续存在的基础;诱导肺组织IκBα表达和抑制NF-κB激活,可能是As₂O₃发挥抗炎作用的重要机制。更多还原

【Abstract】 Objective: Asthma, characterized by eosinophilia, is a chronic inflammatory disease involved in a series of genes with genetic susceptibility. To investigate the effect of arsenic trioxide （As₂O₃） on activation of NF-κB and expression of IκBα in a murine model of asthma, and to explore its possible mechanism for antiinflammation.Methods: Thirty-six BALB/c mice were randomly divided into the control group, the asthmatic group （subdivided into 1, 4, 12 and 24 h timepoints after the last airway challenge of ovalbumin）, and the therapeutic group of As₂O₃ （4 mg/kg）. The characteristic recruitment of eosinophils （EOS） in bronchoalveolar lavage fluid （BALF）, the pulmonary NF-κB activity and IκBα expression were detected by Diff-Quick staining, electrophoretic mobility shift assay （EMSA） and Western blot analysis, respectively. Results: In the control group, the recruitment of EOS in BALE pulmonary NF-κB activity and IκBα expression were （0.56±0.22）%, 51.47±4.53 and 0.80±0.25, respectively. The asthmatic group had higher recruitment of EOS in BALF （P<0.01） and pulmonary NF-κB activity （P<0.01） and lower pulmonary IκBα expression （P<0.01） than did the control group, respectively, in which NF-κB activation was increased within 1h （P<0.01）, peaked by 4 h （P<0.01）, and dissipated by 12 h （P<0.01） to 24 h （P<0.05） after the last airway challenge. In contrast to the asthmatic group, the three parameters changed reversedly significantly （P<0.01） after exposure to As₂O₃, and there was a significant negative correlation between either recruitment of EOS in BALF or pulmonary NF-κB activity and pulmonary IκBα expression （r=-0.82 and -0.94, P<0.01）.Conclusion:、Increased activation of NF-κB might be the basis for chronicity of airway inflammation in asthma. It is a vital mechanism for As₂O₃ to exert its multiple antiinflammation by inhibition of pulmonary NF-κB activation through induction of IκBα expression.更多还原