吲哚胺2,3-双加氧酶在哮喘小鼠肺组织的表达及与γ干扰素的关系

IDO expression in lung tissue and its relationship with IFN-γin asthmatic mice

目的检测小鼠肺组织中吲哚胺2,3-双加氧酶(IDO)的表达和血清及支气管肺泡灌洗液(BALF)中γ干扰素(IFN-γ)的水平,探讨IDO在支气管哮喘发病机制中的作用与IFN-γ的关系。方法选择SPF级BALB/C小鼠21只,随机分成对照组、干预组、哮喘组各7只。尘螨提取液致敏、激发建立小鼠哮喘模型,苏木精-伊红染色观察气道炎症细胞改变,BALF行细胞学分析,ELISA法检测BALF中IFN-γ水平,免疫组织化学、Western Blot检测肺组织IDO蛋白的表达。结果哮喘组:炎症细胞浸润、气道的平滑肌细胞增生、管腔狭窄均明显;干预组:少量炎症细胞侵润,有气道平滑肌细胞的增生,管腔稍狭窄;对照组:无明显变化。哮喘组小鼠BALF中细胞总数、嗜酸性粒细胞数、中性粒细胞数高于干预组及对照组,差异均有统计学意义(P<0.05)。哮喘组血清及BALF中IFN-γ水平低于干预组及对照组,差异均有统计学意义(P<0.05)。哮喘组肺组织IDO灰度值低于对照组及干预组,差异均有统计学意义(P<0.05)。IFN-γ水平在血清中与BALF中呈正相关(P<0.01);肺组织内IDO蛋白的表达与IFN-γ水平在血清中及BALF中均呈正相关(P<0.01)。结论小鼠肺组织中IDO蛋白表达量降低,导致体内免疫耐受缺陷和(或)减弱,促使支气管哮喘的发生发展。

Objective To detect the expression of indoleamine 2,3-dioxygenase(IDO)in lung tissue and the level of interferonγ(IFN-γ)in serum and bronchoalveolar lavage fluid(BALF),and to explore the role of IDO in the pathogenesis of bronchial asthma and its relationship with IFN-γ.Methods Select 21 SPF BALB/C mice.They were randomly divided into control group,intervention group and asthma group,with 7 mice in each group.A mouse model of asthma was established by sensitization and stimulation of dust mites extract.The changes of airway inflammatory cells were observed by hematoxylin-eosin staining;BALF was given cytological analysis;ELISA was used to detect IFN-γlevels in BALF;immunohistochemistry and Western Blot were used to detect IDO protein expression in lung tissue.Results Asthma group:inflammatory cell infiltration,airway smooth muscle cell proliferation and lumen stenosis were obvious;intervention group:there were a small number of inflammatory cells infiltrating,there was airway smooth muscle cell proliferation,and lumen slightly narrowed;control group:there were no significant changes.The total number of cells,eosinophils and neutrophils in the BALF of asthma group were higher than those in the intervention group and the control group(P<0.05).The serum and BALF IFN-γlevels in asthma group were lower than those in intervention group and control group(P<0.05).The IDO gray value of lung tissue in asthma group was lower than that in control group and intervention group(P<0.05).IFN-γlevel in serum was positively correlated with that in BALF(P<0.01),and expression of IDO protein in lung tissue was positively correlated with IFN-γlevel in serum and BALF(P<0.01).Conclusion There is a decrease in IDO protein expression in lung tissue of mice,which leads to deficiency and/or decrease of immune tolerance in vivo and promotes the development of bronchial asthma.