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目的研究三氧化二砷(As2O3)对哮喘小鼠肺组织核因子κB(NF-κB)激活和抑制蛋白IκB-α表达的影响,探讨As2O3抗炎作用的可能机制以及哮喘防治的新思路。方法BALB/c小鼠36只随机分为对照组、哮喘组(卵蛋白末次激发后1,4,12和24h)和As2O3治疗组(4mg/kg),每组6只。Diff-Quick染色观察支气管肺泡灌洗液(bronchoalveolarlavagefluid,BALF)中嗜酸细胞募集特点,电泳迁移率实验和免疫印迹实验分别检测肺组织NF-κB活性和IκB-α表达水平。结果①哮喘组BALF中嗜酸细胞募集[(48.72±5.38)%]较对照组[(0.56±0.21)%]增加(q=33.46,P<0.01),治疗组较哮喘组减少(q=34.65,P<0.01)。②哮喘组肺组织NF-κB活性均较对照组增加(q=41.84,72.75,61.61,16.32,P<0.01或0.05),以4h活性最高,治疗组较哮喘组减少(q=89.48,P<0.01)。③哮喘组肺组织IκB-α表达较对照组减少(q=30.94,P<0.01),治疗组较哮喘组增加(q=23.67,P<0.01)。④BALF中嗜酸细胞募集、肺组织NF-κB活性与IκB-α表达水平均呈负相关(r=-0.82,-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IκB-α表达和抑制NF-κB激活,可能是As2O3发挥广泛抗炎作用的重要机制。
Objective To study the effect of As2O3 on the activation of NF-κB and the expression of IκB-α in lung tissue of asthmatic mice and to explore the possible mechanism of As2O3 anti-inflammatory effect and new ideas of prevention and treatment of asthma. Methods Thirty - six BALB / c mice were randomly divided into control group, asthma group (1, 4, 12 and 24 h after the last challenge of ovalbumin) and As2O3 treatment group (4 mg / kg), 6 in each. Diff-Quick staining was used to observe the characteristics of eosinophil recruitment in bronchoalveolar fluid (BALF). The electrophoretic mobility shift assay and Western blotting were used to detect the expression of NF-κB and IκB-α in lung tissue respectively. Results ① The number of eosinophils in BALF in asthma group was significantly higher than that in asthma group [(48.72 ± 5.38)% vs (0.56 ± 0.21)% vs (q = 33.46, P <0.01) , P <0.01). ② The activity of NF-κB in lung tissue of asthma group was higher than that of control group (q = 41.84,72.75,61.61,16.32, P <0.01 or 0.05), and the activity of NF-κB in the asthma group was the highest at 4h after treatment (q = 89.48, P < 0.01). ③ The expression of IκB-α in lung tissue of asthma group was lower than that of control group (q = 30.94, P <0.01), and the level of IκB-α in asthma group was higher than that of asthma group (q = 23.67, P <0.01). ④ The eosinophil recruitment in BALF was negatively correlated with the expression of NF-κB in lung tissue (r = -0.82, -0.94, P <0.01). Conclusion Overexpression of NF-κB in lung tissue may be the basis of persistence of chronic airway inflammation in asthma. Inducing IκB-α expression and inhibiting the activation of NF-κB in lung tissue may be an important mechanism of As 2 O 3 exerting a wide range of anti-inflammatory effects.