Experimental Study On The Therapeutic Mechanism Of Arsenic Trioxide For Asthma

[Objective] 1. To study the distribution and recruitment of pulmonary dendritic cells (DC), and the influence of arsenic trioxide (As2O3) with three different concentration groups on airway DC of asthmatic mice. 2. To investigate the effect on infiltration of eosinaphils (EOS), apoptosis of EOS and expression of nuclear factor-Kfi (NF-icB) as well as the correlation between infiltration of EOS or expression of NF-KB and apoptosis of EOS in the conducting airways of asthmatic guinea-pigs treated by a low dose of As2O3, and explore the possible therapeutic mechanism of As2O3 for asthma.[Methods] 1. Fifty BALB/c mice were randomly divided into 5 groups: control group, asthmatic group, and therapeutic groups with low dose (Img/kg), moderate dose (5mg/kg) and high dose (lOmg/kg) of As2O3. The immunohistochemistry, scanning electron microscope, and computer-assisted image analysis were applied to detect airway DC. 2. Thirty guinea-pigs were randomly divided into 3 groups: control group, asthmatic group and therapeutic group of As2O3 (2mg/kg). By virtue of characteristic morphology, the TdT-mediated dUTP nick end labeling (TUNEL), immunohistochemistry and computer-assisted image analysis techniques were used to detect airway infiltration of EOS, apoptosis of EOS, andexpression of NF-icB.[Results] 1. All intraepithelial NLDC-145 staining throughout respiratory tree could be accounted for a network of branch tree-like cells in the control mice. The density of DC varied from (500?0) cells/mm2 epithelial surface in the large airways, to (60?0) cells/mm2 epithelial surface in the small airways(P<0.05 ). By scanning electron microscope, we observed DC characteristic of spiny and long processes; Compared with control mice, the density, but not the distribution of airway DC of asthmatic mice was significantly upregulated (P<0.01 ) ; Compared with asthmatic mice, the densities, but not the distributions of airway DC were significantly downregulated among therapeutic groups of As2Os (P<0.01) albeit there were no statistical differences between each other (P>0.05). 2. The bronchial infiltration of EOS was (4.4?.5 ) cells/HP and apoptotic index (AI) of EOS was (0.42?.08)%. All intraepithelial NF-KB staining throughout respiratory tree could be accounted for a network where the density of airway nuclear NF-KB+ staining was (220?2 ) cells/mm2 epithelial surface in the control group; The asthmatic group significantly had a higher amount of infiltrating EOS (P<0.01), a lower AI of EOS (P<0.01), and a higher density of nuclear NF-icB+ cells (P<0.01) than that of control group, respectively; Although there were statistical differences between therapeutic and control groups (P<0.05), the therapeutic group significantly had a lower amount of infiltrating EOS (P<0.01), a higher AI of EOS (P<0.01), and a lower density of nuclear NF-icB+ cells (P<0.01) than that of asthmatic group, respectively.Furthermore, there was a significantly negative correlation not only between airway infiltration of EOS and AI of EOS (r =-0.94 and -0.89, P<0.01), but between AI of EOS and density of nuclear NF-KB+ cells compared with each other (r = -0.93 and -0.91, P<0.01).[Conclusion] 1. There is an integral network of NLDC-145+DC throughout the respiratory tree; It might be an important therapeutic mechanism of As2Oa to downregulate not the distribution but the density of DC in the conducting airways of asthmatic mice. 2. The delayed apoptosis of EOS is an important mechanism for asthma; The delayed apoptosis of EOS is negatively correlated with the increased activation of NF-icB; It might be another important therapeutic mechanism of As2O3 for asthma to decrease activation of NF-icB and increase apoptosis of EOS.