三氧化二砷对哮喘豚鼠肺内核因子-κB表达的影响

Effect of Arsenic Trioxide (As_2O_3) on Expression of Nuclear Factor-kappa B (NF-κB) in the Conducting Airways of Asthmatic Guinea-pigs.

目的：研究Ａｓ２Ｏ３对哮喘豚鼠肺内核因子－κＢ（ｎｕｃｌｅａｒｆａｃｔｏｒ－ｋａｐｐａＢ，ＮＦ－κＢ）表达的影响及其作用机制。方法：豚鼠３０只随机分为３组，即对照组、哮喘组和Ａｓ２Ｏ３（２ｍｇ／ｋｇ）治疗组。采用免疫组织化学染色技术，即小鼠抗大鼠ｐ６５单克隆抗体（Ｆ－６）、生物素化马抗小鼠ＩｇＧ、二氨基联苯胺（ＤＡＢ）显色检测豚鼠气道壁ＮＦ－κＢ；计算机图像分析技术对气道壁ＮＦ－κＢ表达进行定量检测。结果：对照组豚鼠整个肺组织包括气管、支气管、肺泡和脏层胸膜构成了一个ＮＦ－κＢ阳性（ＮＦ－κＢ＋）细胞网络，其中支气管壁胞核ＮＦ－κＢ＋细胞密度为（２２０±７２）／ｍｍ２上皮面积；与对照组相比，哮喘组豚鼠气道壁胞核ＮＦ－κＢ＋细胞密度显著增加（Ｐ＜０．０１）；哮喘豚鼠经Ａｓ２Ｏ３处理后，气道壁胞核ＮＦ－κＢ＋细胞密度显著下降（Ｐ＜０．０１），但与对照组相比仍较高（Ｐ０．０１８）。结论：ＮＦ－κＢ激活增加是支气管哮喘重要的发病机制之一；下调肺内ＮＦ－κＢ激活细胞数量可能是Ａｓ２Ｏ３治疗哮喘的一个重要机制。

Objective:To investigate the effect and mechanism of As_2O_3 on the expression of NF-κB in the conducting airways of asthmatic gu inea-pigs. Methods:Thirty guinea-pigs were randomly divided into 3 groups: control group, asthmatic group and theratputic group of As_2O_3 (2 mg/ kg). The immunohistochemical staining method, namely, mouse anti rat p65 monoclo nal antibody (F-6), biotin-labelled horse anti mouse IgG and DAB-staining tec hnique, was used to detect NF-κB; By virtue of characteristic morphology, we d etected the airway expression of NF-κB with computer image analysis system. Results:All epithelial NF-κB staining throughout the respiratory tre e in the control group could be accounted for a network, and the density of nucl ear NF-κB+ staining was (220±72) cells/mm2 epithelial surface in the con ducting airways; The asthmatic group had a significantly higher density of nucl ear NF-κB+ cells than that of the control group (P＜0.01); There were st atistical differences between the therapeutic group and the control group (P 0.018), but the density of nuclear NF-κB+ cells was significantly decreased in the conducting airways of therapeutic group compared with asthmatic group ( P＜0.01). Conclusion:Our findings suggest that the increased activ ation of NF-κB is an important mechanism of bronchial asthma; the decrement of activated NF-κB+ cells subsequently results in the remission of airway infl amation of therapeutic group, which may be an important therapeutic effect of A s2O3 for asthma.