Experimental Study On The Inhibition Of Asthmatic Airway Inflammation And Airway Remodeling By The New Benzophenone Natural Compound, THBP

Part 1:The Effects of THBP on the Airway Inflammation,Airway Hyperresponsiveness,CD4+CD25+Foxp3+Treg Cells and IDO in Asthmatic MiceObjective:To investigate the effects of THBP on the airway inflammation,airway hyperresponsiveness,CD4+CD25+Foxp3+Treg cells and indoleamine 2,3 dioxygenase(IDO)in asthmatic mice.Methods:24 BALB/c mice were randomly divided into 4 groups,namely,control group,ovalbumin(OVA)group,THBP group and budesonide group.Mice were sensitized and challenged by OVA.24 h after the last challenge,airway responsiveness to acetylcholine chloride(Ach)was measured.Hematoxylin&eosin staining was used to assess the inflammatory cells infiltrating and periodic acid schiff(PAS)to quantify airway global cells.Levels of IL-4 and IL-13 in bronchoalveolar lavage fluid(BALF),and total IgE and OVA-specific IgE(OVA-sIgE)in serum were relevantly detected by ELISA.The percentage of CD4+CD25+Foxp3+Treg cells in the spleen were measured with flow cytometry analysis.The protein expression of IDO was determined by western blot analysis.Results:The airway resistance in the OVA group was obviously increased in a dose-dependent manner by administration of ACh,whereas only a slight increase could be detected in the control group.Treatment with THBP or budesonide led to a sharp decrease in airway resistance compared with the OVA group(P<0.05).Total IgE and OVA-sIgE in serum,total inflammatory cells and differential eosinophils as well as Th2 cytokines in BALF were significantly increased in the OVA group.These inflammatory indices were remarkably decreased by treatment with THBP or budesonide(P<0.05).Treatment with THBP or budesonide increased the ratio of CD4+CD25+Foxp3+Treg cells in the spleen and lung IDO compared with that in the OVA group(P<0.05).Conclusion:THBP could inhibit the airway inflammation and hyperresponsivenes by upregulating the expression of CD4+CD25+Foxp3+Treg cells and IDO.Part 2:The Effects of THBP on the Airway Inflammation and Remodelling in a Murine Model of Chronic AsthmaObjective:To observe the influence of THBP on the airway inflammation and remodelling in a murine model of chronic asthma.Methods:BALB/c mice were randomly divided into four groups,namely,control group,OVA group,THBP group and budesonide group.Mice were sensitized and challenged by OVA.24 h after the last challenge,airway responsiveness to acetylcholine chloride(Ach)was measured.The sections were stained with either hematoxylin&eosin to assess the inflammatory cells infiltrating,periodic acid schiff(PAS)to quantify airway global cells or Masson’s trichrome to determine collagen deposition in the lungs.The expression ofα-SMA and PCNA in lungs was evaluated by immunohistochemistry.The levels of IL-4 and IL-13 in BALF,and total IgE and OVA-sIgE levels in serum were measured by ELISA.Results:The airway resistance in the OVA group was obviously increased in a dose-dependent manner following administration of Ach,whereas only a slight increase could be detected in the control group.Treatment with budesonide led to a sharp decrease in airway resistance compared with the OVA group(P<0.05).Total IgE and OVA-sIgE in serum,total inflammatory cells and differential eosinophils as well as Th2 cytokines in BALF were significantly increased in the OVA group.These inflammatory indices were remarkably decreased by treatment with budesonide(P<0.05).A significant increase in the number of PAS-positive epithelial cells and proliferating cell nuclear antigen(PCNA)-stained smooth muscle,area of Masson’s trichrome staining and a smooth muscle actin(a-SMA)in OVA-sensitized and challenged mice.These indices were obvious decreased by treatment with THBP or budesonide.Conclusion:THBP alleviates the airway inflammation,airway hyperresponsiveness and airway remodelling in a murine model of chronic asthma.