支气管哮喘患者血清MicroRNA-145水平表达与肺功能、气道重塑及Th1/Th2平衡的关系分析

Relationship between Serum MicroRNA-145 Expression with Lung Function,Airway Remodeling and Th1/Th2 Balance in Patients with Bronchial Asthma

目的探讨支气管哮喘(BA)患者血清微小核糖核酸-145(miR-145)表达水平与肺功能、气道重塑、辅助性T细胞1/辅助性T细胞2(Th1/Th2)平衡的关系。方法纳入邯郸市中心医院2018年7月~2020年7月收治的BA患者90例作为BA组,另选取同期于邯郸市中心医院体检的62例健康志愿者作为健康组。比较两组血清miR-145表达水平,肺功能指标[1秒用力呼气容积(FEV1),用力肺活量(FVC),FEV1/FVC,峰值呼气流速(PEF)和最大呼气中期流量(MMEF75/25)],气道重塑指标[气道总面积(Ao),气道腔面积(Ai),气道外径(D),气道内径(L),支气管管壁厚度与外径比值(T/D)和气道壁面积占气道总截面积百分比(WA%)],Th1和Th2,并计算二者比值Th1/Th2。比较两组Th1和Th2细胞生成的主要因子[干扰素-γ(IFN-γ),白介素-4(IL-4)]和T细胞亚群(Tc1,Tc2)水平,分析血清miR-145表达水平与肺功能、气道重塑及Th1,Th2细胞以及IFN-γ,IL-4,Tc1,Tc2水平的相关性。结果BA组血清miR-145表达水平较健康组明显升高,而FEV1,FVC,PEF,MMEF75/25,FEV1/FVC较健康组明显下降,差异均有统计学意义(t=7.252~56.696,均P<0.05)。BA组D,Ao,T/D和WA%高于健康组,差异均有统计学意义(t=5.687~21.897,均P<0.05),且BA组Th1,Th1/Th2,Tc1,Tc1/Tc2和IFN-γ较健康组显著降低,而Th2,Tc2,IL-4高于健康组(t=8.054~25.194,均P<0.05)。血清miR-145表达水平与FEV1,FVC,PEF,MMEF75/25,FEV1/FVC,Th1,Th1/Th2,IFN-γ,Tc1,Tc1/Tc2呈负相关(r=-0.711~-0.403,均P<0.05),与D,Ao,T/D,WA%,Th2,IL-4和Tc2呈正相关(r=0.409~0.624,均P<0.05)。结论BA患者的血清miR-145表达水平明显上调,其表达与患者肺功能、气道重塑以及Th1/Th2存在一定关系,临床可以考虑将其作为治疗支气管哮喘的新靶点。

Objective To explore the relationship between serum MicroRNA-145(miR-145)with lung function,airway remodeling and helper T cells 1/helper T cells 2(Th1/Th2)in patients with bronchial asthma(BA).Methods 90 patients with BA admitted to Handan Central Hospital from July 2018 to July 2020 were included as the BA group,and 62 healthy volunteers who received physical examination in Handan Central Hospital during the same period were selected as the healthy group.The expression level of serum miR-145 and pulmonary function indexes[forced expiratory volume in one second(FEV1),forced vital capacity(FVC),FEV1/FVC,peak expiratory flow(PEF),maximal mediate expiratory flow(MMEF75/25)],airway remodeling index[total airway crosssectional area(Ao),area of airway(Ai),external diameter(D),lumen diameter(L),airway wall thickness/external diameter(T/D),percentage of wall area(WA%)]and Th1,Th2 of two groups were compared,the ratio of the two Th1/Th2 was calculated.The levels of main factors[interferon-γ(IFN-γ),interleukin-4(IL-4)]and T cell subsets(Tc1,Tc2)were compared between the two groups.The correlation between serum miR-145 expression and lung function,airway remodeling,Th1,Th2 cells,IFN-γ,IL-4,Tc1,Tc2 levels were analyzed.Results The expression level of serum miR-145 in the BA group was significantly higher than that in the healthy group,while FEV1,FVC,PEF,MMEF75/25,FEV1/FVC were significantly lower than those in the healthy group,the difference were statistically significant(t=7.252~56.696,all P<0.05).The levels of D,Ao,T/D and WA%in BA group were higher than those in healthy group,the difference were statistically significant(t=5.687~21.897,all P<0.05),and the levels of Th1,Th1/Th2,Tc1,Tc1/Tc2 and IFN-γin BA group were significantly lower than those in healthy group,while the levels of Th2,Tc2 and IL-4 in BA group were higher than those in healthy group,the difference were statistically significant(t=8.054~25.194,all P<0.05).The expression level of serum miR-145 were negatively correlated with FEV1,FVC,PEF,MMEF75/25 and FEV1/FVC,Th1,Th1/Th2,IFN-γ,Tc1,Tc1/Tc2(r=-0.711~-0.403,all P<0.05),and positively correlated with D,Ao,T/D,WA%,Th2,IL-4 and Tc2(r=0.409~0.624,all P<0.05).Conclusion The expression level of serum miR-145 in BA patients was significantly up-regulated,and its expression was correlated with lung function,airway remodeling and Th1/Th2.It can be considered as a new target for the treatment of bronchial asthma.