转录因子在孟鲁司特钠治疗类固醇激素抵抗型变应性鼻炎中的作用

摘要

目的：研究外周血单个核细胞中转录因子活化蛋白-1(AP-1)及核因子-资B(NF-资B)在孟鲁司特钠治疗类固醇激素抵抗型变应性鼻炎(AR)中的作用。方法筛选50例类固醇激素抵抗型AR患者，随机分成两组，分别口服孟鲁司特钠片(孟鲁司特钠组)或ATP片(安慰剂组)治疗，治疗21 d后，对两组患者进行症状和体征记分，应用EMSA法测定外周血中AP-1及NF-资B的DNA结合活性，ELISA法测定血清IL-4、IL-5及IL-10的表达水平。结果治疗21 d后，孟鲁司特钠组治疗有效率显著高于安慰剂组(P<0.01)；与安慰剂组比较，孟鲁司特钠组AP-1和NF-资B的DNA结合活性明显降低(P<0.01)；孟鲁司特钠组症状与体征总积分下降指数(SRI)与AP-1及NF-资B的DNA结合活性呈负相关(P<0.05)，而安慰剂组两者间无明显相关关系(P>0.05)；经治疗后孟鲁司特钠组患者血清IL-4、IL-5水平较安慰剂组显著降低，而IL-10水平较安慰剂组显著升高(P<0.01)。结论孟鲁司特钠可能通过抑制外周血单个核细胞中转录因子AP-1及NF-资B的转录活性，调节细胞因子IL-4、IL-5及IL-10的表达，改善类固醇激素抵抗型AR患者病情，发挥抗炎作用。%Objective To investigate the function of activator protein-1(AP-1)and nuclear factor-κB(NF-κB)on the treatment of montelukast sodium tables for patients with steroid-resistant allergic rhinitis (AR). Methods A random-ized study was carried out in 50 patients with steroid-resistant AR. 25 cases were treated with montelukast sodium ta-bles(montelukast sodium group), and the others by ATP tables(placebo group). Score system was used to compare the therapeutic effect of these two drugs on clinical symptoms and signs on 21th day after therapy. The DNA binding activ-ities of Ap-1 and NF-κB were measured by electrophoretic mobility shift assay(EMSA). The expression of IL-4, IL-5 and IL-10 were determined by enzyme-linked immunoadsorbent assay (ELISA). Results The therapeutic effect rate in montelukast sodium group was significantly higher than that in placebo group at 21 days after treatment begining (P<0.01). Compared with placebo group, the DNA binding activities of Ap-1 and NF-κB were significantly reduced in montelukast sodium group (P<0.01). The score reduce index (SRI)of the clinical symptoms and signs was negatively correlated with the DNA binding activities in montelukast sodium group (P<0.05), but there was any correlation be-tween them in placebo group(P>0.05).The expression of IL-4 and IL-5 in montelukast sodium group were significantly lower and IL-10 was higher than those in placebo group (P<0.01). Conclusion The treatment effect of montelukast sodium tables for steroid-resistant AR may be aroused by suppressing the Ap-1 and NF-κB DNA binding activities, and effecting the expression of IL-4, IL-5 and IL-10.