血红素加氧酶-1对哮喘模型中Th1/Th2/Th17/Treg亚群及相关细胞因子分泌格局的影响OACSTPCD

Objective To explore the effect of heme oxygenase-1(HO-1)on Th1/Th2/Th17/Treg subsets and the secretion pattern of related cytokines in asthmatic mouse model.Methods Balb/C mice were randomly divided into five groups:normal control group,ovalbumin(OVA)group,heme chloride(Hemin)group,tin protoporphyrin(SnPP)group,and Hemin+SnPP group,with 10 mice in each group.The mice in OVA group were sensitized and challenged to establish an asthma model,and the mice in the other three groups were intraperitoneally injected with Hemin,SnPP,Hemin+SnPP solution at day 2 before OVA sensitization and challenge and at day 27 respectively.Airway inflammation degree was detected by bronchoalveolar lavage fluid(BALF)cell counting and lung histo-pathology.The proportions of CD4+CD25+FoxP3+Treg,CD4+IL-10R+IFN-γR+Treg1 and CD4+IL-17+Th17 in splenic cells were mea-sured by flow cytometry,the levels of IL-4,IFN-γ,IL-2,IL-17,TNF-α,IL-10 and TGF-β in serum and BALF were analyzed by ELISA,and the expression of IL-17 in lung tissue was detected by immunohistochemistry.Results ①Compared with normal control group,there were different degrees of inflammatory cell infiltration in the lung tissues in the other four groups,and it was the most severe in OVA group,and the lightest in Hemin group.Compared with normal control group,the numbers of total cells and eosinophils(EOS)in BALF were significantly increased in OVA group,the proportion of CD4+CD25+FoxP3+Treg cells in spleen tissue was de-creased,the proportion of CD4+IL-17+Th17 cells was increased,serum levels of IL-4 and TNF-α were increased,and serum levels of IFN-γ,IL-2,IL-10 and TGF-β were decreased,IL-17 level in BALF was increased,and the positive expression of IL-17 in lung tissue was increased(all P<0.01).Compared with normal control group,the numbers of total cells and EOS in BALF,and the propor-tions of CD4+CD25+FoxP3+Treg,CD4+IL-10R+IFN-γR+Treg1 and CD4+IL-17+Th17 cells were increased in Hemin group(all P<0.01),and the other indexes showed no significant change.Compared with normal control group,CD4+CD25+FoxP3+Treg proportion and IL-10 level in Hemin+SnPP group and TNF-α level in SnPP group and Hemin+SnPP group showed no significant changes,and the change trend of the other indexes was the same as those in OVA group(all P<0.01).②Compared with OVA group,the infiltration of inflammatory cells in lung tissue was reduced in Hemin group,the numbers of total cells and EOS in BALF were significantly decreased,the proportions of CD4+CD25+FoxP3+Treg and CD4+IL-10R+IFN-γR+Treg1 cells in the spleen were increased,and the proportion of CD4+IL-17+Th17 cells was decreased(all P<0.01),and the changes of other cytokines except TGF-β showed significant changes(P<0.05),and the change trend of all the indexes in the other two groups was the same as those in OVA group.Compared with Hemin group,the immune imbalance and the changes of inflammatory factors were more obvious in SnPP group and Hemin+SnPP group.Conclusions Heme oxygenase-1 can affect the differentiation and function of Th1/Th2/Th17/Treg cell subsets and the secretion pattern of related cytokines,and exert immunoregulatory function in asthmatic model.