支气管哮喘患儿血清miR-125a表达与气道重塑的相关性

Correlation between serum miR-125a expression and airway remodeling in children with bronchial asthma

目的探讨支气管哮喘患儿血清miR-125a表达与气道重塑的相关性。方法选取2020年1月—2022年12月张家口市第四医院支气管哮喘患儿231例(哮喘组)和体检健康儿童231名(正常对照组)。检测所有研究对象血清miR-125a相对表达量和肺功能指标[第1秒用力呼气容积(FEV1)、用力肺活量(FVC)、FEV1占FVC的百分比(FEV1/FVC%)]、气道重塑指标[气道内径(L)、气道外径(D)、气道总面积(Ao)、气道腔面积(Ai)、支气管管壁厚度(T)/D比值、气道壁面积占气道总截面积的百分比(WA%)]、气道重塑相关血清学指标[转化生长因子-β1(TGF-β1)、骨桥蛋白(OPN)、基质金属蛋白酶-9(MMP-9)]。采用Pearson相关分析评估各项指标之间的相关性。采用受试者工作特征(ROC)曲线评价miR-125a判断支气管哮喘患儿病情的效能。采用Logistic回归分析评估支气管哮喘患儿病情加重的危险因素。结果与正常对照组比较,哮喘组血清miR-125a相对表达量和FEV1、FVC、FEV1/FVC%均降低(P<0.05),D、Ao、T/D比值、WA%和血清TGF-β1、OPN、MMP-9水平均升高(P<0.05);2个组之间L、Ai差异均无统计学意义(P>0.05)。哮喘组miR-125a与FEV1、FVC、FEV1/FVC%均呈正相关(r值分别为0.342、0.373、0.465,P<0.01),与D、Ao、T/D比值、WA%、TGF-β1、OPN、MMP-9均呈负相关(r值分别为–0.226、–0.458、–0.301、–0.388、–0.394、–0.452、–0.429,P<0.05),与L和Ai无相关性(r值分别为0.079、0.094,P>0.05)。正常对照组miR-125a与其他指标均无相关性(P>0.05)。急性发作期组miR-125a相对表达量显著低于临床缓解期组(P<0.001),TGF-β1、OPN、MMP-9水平显著高于临床缓解期组(P<0.001)。轻度组、中度组、重度组miR-125a相对表达量依次降低(P<0.001),TGF-β1、OPN、MMP-9水平依次升高(P<0.001)。miR-125a诊断重度支气管哮喘的ROC曲线下面积(AUC)为0.831。TGF-β1≥367.20 ng·L^(–1)、MMP-9≥123.19μg·L^(–1)、miR-125a≤0.34是患儿支气管哮喘急性发作的危险因素(P<0.05)。结论支气管哮喘患儿血清miR-125a水平显著降低,且与患儿肺功能和气道重塑密切相关,或可作为支气管哮喘患儿病情评估的指标。

Objective To investigate the correlation between serum miR-125a expression and airway remodeling in children with bronchial asthma.Methods A total of 231 children with bronchial asthma(asthma group)and 231 healthy children(healthy control group)were enrolled from January 2020 to December 2022.The relative expression level of serum miR-125a,pulmonary function indicators[forced expiratory volume in one second(FEV1),forced vital capacity(FVC),the percentage of FEV1 of FVC(FEV1/FVC%)],airway remodeling indicators[airway inner diameter(L),airway outer diameter(D),airway cross-sectional area(Ao),airway cavity area(Ai),airway wall thickness(T)/D ratio,the percentage of airway wall area to total airway crosssectional area(WA%)],serological indicators related to airway remodeling[transforming growth factor-beta1(TGF-β1),osteopontin(OPN),matrix metalloproteinase-9(MMP-9)]were determined.Pearson correlation analysis was used to evaluate the correlation among the indicators.Receiver operating characteristic(ROC)curve was used to evaluate the efficacy of miR-125a in the diagnosis of children with bronchial asthma.Logistic regression analysis was used to evaluate the risk factors of exacerbation in children with bronchial asthma.Results Compared with healthy control group,the relative expression level of serum miR-125a,FEV1,FVC and FEV1/FVC%in asthma group were decreased(P<0.05),while the levels of D,Ao,T/D ratio,WA%and serum TGF-β1,OPN and MMP-9 were increased(P<0.05).There was no statistical significance in L and Ai between the 2 groups(P>0.05).The miR-125a was positively correlated with FEV1,FVC and FEV1/FVC%in asthma group(r values were 0.342,0.373 and 0.465,P<0.01).It was negatively correlated with D,Ao,T/D ratio,WA%,TGF-β1,OPN and MMP-9 levels(r values were–0.226,–0.458,–0.301,–0.388,–0.394,–0.452 and–0.429,P<0.05).There was no correlation with L and Ai(r values were 0.079 and 0.094,P>0.05).There was no correlation between miR-125a and other indicators in control group(P>0.05).The relative expression level of miR-125a in acute attack group was lower than that in clinical remission group(P<0.001),while the levels of TGF-β1,OPN and MMP-9 were higher than those in clinical remission group(P<0.001).The relative expression of miR-125a in mild,moderate and severe groups was decreased successively(P<0.001).The levels of TGF-β1,OPN and MMP-9 were increased successively(P<0.001).The area under curve(AUC)of miR-125a for the diagnosis of severe bronchial asthma was 0.831.TGF-β1≥367.20 ng·L^(–1),MMP-9≥123.19μg·L^(–1),miR-125a≤0.34 were risk factors for acute attack in children with bronchial asthma(P<0.05).Conclusions Serum miR-125a level is decreased in children with bronchial asthma,and it is related to lung function and airway remodeling in children with bronchial asthma,which may be used as an indicator to evaluate the condition of children with bronchial asthma.