血清β2-AR mRNA和NGF mRNA水平检测在儿童支气管哮喘气道重塑中的应用价值

Clinic Application of Levels of Serum β2-AR mRNA and NGF mRNA for Children with the Bronchial Asthma in Airway Remodeling

目的探讨血清β2-肾上腺素受体(β2-AR)mRNA和组织神经生长因子(NGF)mRNA水平的检测在儿童支气管哮喘气道重塑中的应用价值。方法收集2015年3月～2017年3月在咸阳市第一人民医院儿科门诊就诊或住院的33例发生气道重塑的支气管哮喘患儿的血液及临床资料,并选取29例呼吸系统炎症疾病患儿作为对照组,采用实时荧光定量PCR(Real-time-PCR,RT-PCR)技术检测患儿治疗前后血清β2-AR mRNA和NGF mRNA的表达。比较分析血清β2-AR mRNA和NGFmRNA的变化与哮喘重塑发生之间的关系。采用高分辨螺旋CT,测量受试者气道的内径(L)、外径(D),通过公式T=(D-L)/2计算气道壁的厚度(T),测量气道腔面积(AI)、气道总横截面积(AO),通过以上指标评价哮喘气道重塑的发生。采用受试者工作特征曲线(ROC曲线)评价血清β2-AR mRNA和NGF mRNA的临床意义。结果与对照组比较,治疗后组的血清β2-AR mRNA水平下调和NGF mRNA水平上调,其差异均有统计学意义(t=37.27,36.53,均P<0.01)。与治疗前组比较,治疗后组的血清β2-AR mRNA和NGF mRNA水平下调,其差异均有统计学意义(t=7.95,12.67,均P<0.01)。治疗后组血清β2-AR mRNA和NGF mRNA水平呈现负相关性(r=-0.697,P<0.01),该组两标志物分别与气道内径(L),气道壁的厚度(T)及气道腔面积(AI)有明显相关性(r=0.775,-0.780,0.793,均P<0.01),(r=-0.750,0.763,-0.779,均P<0.01)。治疗前组血清β2-AR mRNA和NGFmRNA水平呈现负相关性(r=-0.703,P<0.01),该组两标志物分别与气道内径(L),气道壁的厚度(T)及气道腔面积(AI)有明显相关性(r=0.782,-0.797,0.803,均P<0.01),(r=-0.772,0.787,-0.809,均P<0.01)。血清β2-AR mRNA和NGF mRNA在治疗后表达量的AUC分别为0.767(95%CI:0.658～0.876,P=0.000);0.744(95%CI:0.632～0.856,P=0.000)。根据SPSS统计结果计算出β2-AR和NGF在最佳临界值处诊断重塑的敏感度和特异度分别为93.9%和96.2%,92.9%和95.7%。结论检测血清β2-AR mRNA和NGF mRNA水平可应用于儿童支气管哮喘气道重塑疗效的评价,估计病情的发展状况,并为哮喘患儿的早期干预治疗、有效控制气道炎症及逆转哮喘病程进展提供依据。

Objective To investigate the clinical application value of detection of serum beta 2 adrenergic receptor（beta 2-AR） mRNA and nerve tissue growth factor （NGF） mRNA in airway remodeling on children with bronchial asthma. Methods The clinical serum data of 33 cases of children with bronchial asthma in airway remodeling were selected, divided into the pre-treatment group and the post-treatment group,and selected 29 cases of children with respiratory diseases as the control group. The above research subjects were outpatients or inpatients from department of pediatrics in the First People＇s Hospital of Xianyang City from 2015.3 to 2017.3. The expression of sfrum beta 2-ARmRNA and NGFmRNA were detected by real-time fluorescence quantitative PCR （Real-time-PCR, RT-PCR）. The relationship between the changes of serum 2-ARm- RNA and NGFmRNA and the occurrence of asthma remodeling was compared and analyzed. All the subjects were measured the inner diameter of the airway （L） ,diameter of the airway （D）,the airway wall thickness （T） calculated by T-----（D--L）/ 2, the airway lumen area （AI）, total airway cross-sectional area （AO） with High Resolution Computerized Tomography in evaluation of airway remodeling of asthma through the above indexes. The clinical significance of serum beta 2-ARmRNA and NGFmRNA by receiver operating characteristic curve （ROC curve） was evaluated. Results The serum beta 2-ARmRNA and NGFmRNA expression in the post-treatment group were, respectively, up-regulation and down-regulation in comparison with the pre-treatment group, and there was significant difference （t = 37.27,36.53, all P〈 0.01 ）, which in the post-treat- ment group were, respectively, down-regulation and up -regulation in comparison with the control group,and there was significant difference （t = 7.95,12.67, all P〈0.01）. The expression of erum beta 2-ARmRNA and NGFmRNA had a negativecorrelation in the remodeling group （r=-0. 697,P〈0.01）, which was associated obviously respectively with L, T and AI （r=0. 775,-0. 780,0. 793,all P〈0.01）, （r= - 0. 750,0. 763, - 0. 779, all P〈0.01）. The expression of erum beta 2- ARmRNA and NGFmRNA had a negative correlation in the pre-treatment group （r=-0. 703, P〈0.01 ）, which was associ ated obviously respectively with L,T and AI （r=0. 782,--0. 797,0. 803,all P〈0.01）,（r=-0. 772,0. 787-0. 809,all P 〈0.01）. According to the statistical results of SPSS,ROC curve analysis showed that the expression levels of serum beta 2- ARmRNA and NGFmRNA in the remodeling group were 0. 767（95% CI：0. 65840. 876,P=0. 000） ;0. 744（95%CI：0. 632 40. 856,P=0. 000）. The sensitivity and specificity of beta 2-ARmRNA and NGF mRNA at the optimal critical value were 93.90//00 and 96.2 % ,92.90% and 95.7 %. Conclusion The expression of serum beta 2-ARmRNA and NGFmRNA can monitor treatment of airway remodeling on children bronchial asthma, and estimate disease development, effectively control the progress of airway inflammation in reversing asthma disease progression to provide the basis for early intervention of children with bronchial asthma.