不同浓度三氧化二砷对哮喘小鼠气道树突状细胞的作用

目的 :研究 3种不同浓度三氧化二砷 (arsenictrioxide,As2 O3)对哮喘小鼠气道树突状细胞 (dendriticcells ,DCs)分布和募集的作用。方法 :BALB c小鼠 5 0只随机分为5组 ,即对照组、哮喘组、低剂量 (1mg kg)As2 O3组、中剂量 (5mg kg)As2 O3组和高剂量 (10mg kg)As2 O3组。采用免疫组织化学染色、计算机图像分析和扫描电镜技术分别检测气道DCs。结果 :对照组小鼠整个肺组织构成了一个NLDC 14 5 +DCs网络 ,NLDC 14 5 + DCs密度从大气道到小气道分别为(5 0 0± 5 0 )个 mm2 到 (6 0± 10 )个 mm2 上皮面积 (P <0 0 5 ) ;哮喘组小鼠肺内NLDC 14 5 + DCs密度较对照组显著增加 (P <0 .0 1) ,但不影响其肺内分布 ;哮喘小鼠经As2 O3处理后 ,肺内NLDC 14 5 + DCs密度显著下降 (P <0 0 1) ,但不影响其肺内分布 ,且三种不同浓度砷剂处理组间无显著性差异 (P >0 0 5 )。结论 :下调肺内DCs密度而不影响其肺内分布 ,可能是As2 O3治疗哮喘的一个重要机制 ;低剂量As2 O3治疗哮喘具有潜在的应用前景。

Effect of Arsenic Trioxide with Various Concentrations on Dendritic Cells in the Conducting Airways of Asthmatic Mice

Objective: To investigate the effect of arsenic trioxide (As2 O3 )with three different concentration groups on the distribution and recruitment of dendritic cells(DCs)in the conducting airways of asthmatic mice. Meth ods: Fifty BALB/c mice were divided into 5 groups at random: control group, asthmatic group, therapeutic groups with low dose( 1 mg/kg), moderate dose ( 5 mg/kg) and high dose ( 10 mg/kg) of As2O3. The immunohistochemistry, scanning electron microscope and computerized image analysis were applied to detect airway DCs, respectively. Results: We demonstrated from the control mice that all intraepitheliai NLDC-145+ DCs throughout the respiratory tree could be ac counted for a network of cells with dendritic cell morphology, and the density of DCs varied from(500 + 50)cells/mm2 ep ithelial surface in the large airways, to(60 ± 10) cells/mm2 epithelial surface in the small airways(P ＜ 0.05). The DCs characteristic of spiny and long processes were impressively observed by the scanning electron microscope. Compared with the control mice, the density, but not the distribution of NLDC-145+ DCs was significantly upregulated in the con ducting airways of asthmatic mice( P ＜ 0.01). Compared with the asthmatic mice, the densities, but not the distributions of NLDC-145+ DCs were significantly down regulated in the conducting airways of the therapeutic groups with three varying concentrations of As2O3 ( P ＜ 0.01) while there were no statistical differences between each other ( P ＞ 0.05).Conclusion: Our findings suggest that it might be an important therapeutic mechanism of As2O3 to downregniate not the distribution but the density of DCs in the conducting airways of asthmatic mice, and low dose of As2O3 has potential val ue in treating asthma.