1 深圳市龙华区中心医院儿科，广东 深圳 518110
目的：探讨去整合素金属蛋白酶8(disintegrins metalloproteinase 8，ADAM8)、干扰素调控因子1(interferon regulatory factor 1，IRF1)在支气管哮喘患儿外周血中的表达水平及其临床意义。方法：选取2015年3月至2017年3月在我院诊治的83例支气管哮喘患儿为研究对象，根据全球哮喘防治倡议(Global Initiative for Asthma，GINA)分为轻度持续组47例，中度持续组19例，重度持续组17例，同期选取35例健康儿童作为对照组。采用荧光定量PCR(fluorescent quantitative PCR，qRT-PCR)法检测各组儿童外周血中ADAM8，IRF1 mRNA水平；采用Western印迹检测各组儿童外周血中ADAM8，IRF1蛋白水平；采用肺功能仪检测各组儿童肺功能；分析ADAM8，IRF1蛋白水平与肺功能的相关性。结果：与对照组比较，哮喘患儿外周血中ADAM8，IRF1 mRNA和蛋白水平均显著上调(P<0.05)，中重度哮喘患儿外周血中ADAM8，IRF1 mRNA和蛋白水平明显高于轻度患儿(P<0.05)。哮喘患儿外周血中ADAM8与IRF1的表达呈正相关(r=0.815，P<0.05)。哮喘患儿外周血中ADAM8，IRF1蛋白表达水平与第1秒用力呼气量(forced expiratory volume in 1 second，FEV1)、第1秒用力呼气量与用力肺活量比值(forced expiratory volume in 1 second and forced vital capacity ratio，FEV1/FVC)、用力呼气峰值流速(force expiratory peak velocity，PEF)等肺功能指标均呈负相关(P<0.05)。结论：ADAM8，IRF1在哮喘患儿外周血中高表达，与肺功能呈负相关，具有协同致炎作用，提示ADAM8，IRF1可作为临床上评估哮喘病情发展的参考指标，推测二者可作为治疗哮喘的新靶点。关键词： 支气管哮喘；去整合素金属蛋白酶8；干扰素调控因子1；儿童；肺功能
ADAM8 and IRF1 expression levels in peripheral blood of children with bronchial asthma and clinical significance
Foundation: This work was supported by Shenzhen Science and Technology Plan Project, China (JCY20150403150555531).
Objective: To explore disintegrins metalloproteinase 8 (ADAM8) and interferon regulatory factor 1 (IRF1) expression levels in peripheral blood of children with bronchial asthma and clinical significance. Methods: A total of 83 cases of children with bronchial asthma treated in our hospital from March 2015 to March 2017 were selected as the study objects and divided into a mild persistent group (n=47), a moderate group (n=19), and a severe group (n=17) according to Global Asthma Initiative (GINA); 35 healthy children in the same period were as the control group. ADAM8 and IRF1 mRNA levels in peripheral blood of children in each group were detected by fluorescent quantitative PCR (qRT-PCR), ADAM8 and IRF1 protein levels in peripheral blood of children in each group were tested by Western blot, lung function in each group was tested by lung function tester. The relevance of ADAM8, IRF1 protein levels and lung function was analyzed. Results: Compared with those in the control group, ADAM8, IRF1 mRNA and protein levels in peripheral blood of asthmatic children significantly increased (P<0.05). ADAM8, IRF1 mRNA and protein levels in peripheral blood of children with moderate and severe asthma were significantly higher than those of mild children (P<0.05). ADAM8, IRF1 mRNA and protein levels in peripheral blood of asthmatic children were negatively correlated with the forced expiratory volume in 1 second (FEV1), forced expiratory volume in 1 second and forced vital capacity ratio (FEV1/FVC), forced peak expiratory flow (PEF) and other lung function indexes. Conclusion: ADAM8 and IRF1 high expression in peripheral blood of asthmatic children is negatively related to lung function, with synergistic proinflammatory effect. It is suggested that ADAM8 and IRF1 can be used as reference indexes for evaluating the development of asthma in clinic, and the two can be used as a new target for asthma treatment.Keywords： bronchial asthma; integrin metalloproteinase 8; interferon regulatory factor 1; children; pulmonary function