哮喘患者血清miR-133a、CTGF表达变化及与气道炎症、重塑的相关性分析

Changes of serum miR-133a and CTGF expressions in asthmatic patients and their correlations with airway inflammation and remodeling

目的检测哮喘患者血清miR-133a、结缔组织生长因子(CTGF)表达变化并探讨其与哮喘患者气道炎症、气道重塑的相关性。方法回顾性收集2017年1月至2019年2月在重庆市巴南区人民医院确诊的153例哮喘患者作为研究对象,其中哮喘急性发作期患者77例、缓解期76例,并选取62例健康体检者作为对照组。采集空腹静脉血,采用荧光定量PCR法检测血清miR-133a水平,采用酶联免疫吸附实验(ELISA)法检测血清CTGF水平以及炎症因子白细胞介素(IL)-5、肿瘤坏死因子-α(TNF-α)、IL-4水平,用高分辨螺旋CT测量受试者气道的内径(L)、外径(D),计算气道壁厚度(T),测量气道腔面积(AI),并对miR-133a、CTGF的表达量与气道重塑指标、气道炎症分子进行相关性分析。结果与对照组相比,缓解期组、急性期组哮喘患者FEV1、FEV1/FVC、气道重塑指标L、AI及血清miR-133a表达水平依次降低,气道T及血清CTGF、IL-5、TNF-α、IL-4表达水平依次增加,差异均有统计学意义(P<0.05)。经Pearson法分析显示,哮喘患者外周血血清miR-133a表达水平与血清中IL-5、TNF-α、IL-4表达水平、气道重塑指标T均呈负相关(r=-0.605、-0.537、-0.614,-0.557,P<0.05),与气道重塑指标L、AI均呈正相关(r=0.563、0.514,P<0.05);哮喘患者外周血血清CTGF表达水平与血清中IL-5、TNF-α、IL-4表达水平、气道重塑指标T呈正相关(r=0.568、0.527、0.611,0.604,P<0.05),与气道重塑指标L和AI均呈负相关(r=-0.612、-0.531,P<0.05)。结论哮喘患者血清miR-133a表达下调、CTGF表达上调,二者与气道炎症、气道重塑均具有一定相关性,可能为临床治疗和控制哮喘提供一定参考。

Objective To detect the changes of serum miR-133a and connective tissue growth factor(CTGF)expressions in asthmatic patients and to explore their correlations with airway inflammation and airway remodeling in asthmatic patients.Methods A total of 153 asthmatic patients diagnosed in People's Hospital of Chongqing Banan District from January 2017 to February 2019 were selected as the study objects,including 77 patients in acute attack phase,76 patients in remission phase and 62 healthy people were selected as the control group,the fasting venous blood was collected,the level of miR-133a in serum was detected by fluorescence quantitative PCR,the levels of serum CTGF,inflammatory factor interleukin(IL)-5,tumor necrosis factor-α(TNF-α)and IL-4 were measured by enzyme-linked immunosorbent assay(ELISA),the inner diameter(L)and outer diameter(D)of airway were measured by high resolution spiral CT,the airway wall thickness(T)was calculated,the airway cavity area(AI)was measured,and the relationships between the expressions of miR-133a and CTGF and airway remodeling index and airway inflammatory molecules were analyzed.Results Compared with the control group,the FEV1,FEV1/FVC,airway remodeling indexes L,AI and expression levels of serum miR-133a of asthma patients in remission group and acute phase group decreased in turn,and the airway remodeling index T and expression levels of serum CTGF,IL-5,TNF-α,IL-4 increased in turn,the differences were statistically significant(P<0.05).Pearson's analysis showed that the expression level of miR-133a in peripheral blood of asthmatic patients was negatively correlated with the expression levels of IL-5,TNF-α,IL-4 and airway remodeling index T(r=-0.605,-0.537,-0.614,-0.557,P<0.05),and positively correlated with airway remodeling indexes L and AI(r=0.563,0.514,P<0.05);the expression of serum CTGF in peripheral blood of asthmatic patients was positively correlated with the expressions of IL-5,TNF-α,IL-4 and airway remodeling index T(r=0.568,0.527,0.611,0.604,P<0.05),and negatively correlated with airway remodeling indexes L and AI(r=-0.612,-0.531,P<0.05).Conclusion The expression of miR-133a is down-regulated in asthmatic patients,and the expression of CTGF is up-regulated,they are related to airway inflammation and airway remodeling,which may provide some reference for clinical treatment and control of asthma.