Notch1和PTEN在儿童支气管哮喘中的意义

目的探讨Notch1和磷酸酯酶和张力蛋白同源物基因(PTEN)在儿童支气管哮喘中的作用及意义。方法选取2015年1月-2018年1月河南某医院诊治的41例支气管哮喘患儿(观察组)及同期在该院进行健康体检的40例儿童(对照组)作为研究对象。检测研究对象肺功能指标一秒用力呼气容积(FEV 1)、FEV 1/用力肺活量(FVC)、用力呼气中期流速(FEF25%~75%)、用力呼气50%肺活量的瞬间流速(FEF50%)、用力呼气75%肺活量的瞬间流速(FEF75%)、呼出气一氧化氮(FeNO)]、白细胞介素-6(IL-6)和嗜酸性粒细胞(Eos)水平,qRT-PCR检测Notch1和PTEN mRNA表达水平,将所得数据进行统计分析。结果观察组研究对象的FEV 1,FEV 1/FVC,FEF25%~75%,FEF50%及FEF75%分别为(1.38±0.65)L,(60.35±10.42)%,(3.15±1.23)L/s,(1.76±0.79)L/s及(0.78±0.54)L/s,均低于对照组的(2.47±0.53)L,(79.46±13.26)%,(4.09±1.57)L/s,(2.57±1.03)L/s及(1.25±0.38)L/s(均P<0.05)。观察组研究对象的FeNO为(17.35±11.53)ppb,高于对照组的(10.46±4.25)ppb(P<0.05)。观察组研究对象的Eos及IL-6分别为(0.36±0.13)×10^9/L及(0.73±0.17)ng/mL,均高于对照组的(0.16±0.11)×10^9/L及(0.38±0.14)ng/mL(均P<0.05)。观察组研究对象的Notch1 mRNA水平为1.52±0.13,明显高于对照组的0.87±0.09(P<0.05);观察组研究对象的PTEN mRNA水平为0.38±0.08,明显低于对照组的1.17±0.19(P<0.05)。相关性分析结果显示,Notch1 mRNA的表达水平与FEV 1,FEV 1/FVC,FEF25%~75%,FEF50%及FEF75%等指标呈现负相关(均P<0.05),与FeNO,IL-6和Eos等指标呈正相关(均P<0.05)。而PTEN mRNA的表达水平与FEV 1,FEV 1/FVC,FEF25%~75%,FEF50%及FEF75%等指标呈现正相关(均P<0.05),与FeNO,IL-6和Eos呈负相关(均P<0.05)。且Notch1 mRNA的表达与PTEN mRNA的表达呈现负相关(P<0.05)。结论哮喘患儿体内Notch1水平上调,Notch1可通过抑制PTEN表达及促进IL-6等炎症分子表达,诱导哮喘的发生和进展。

Significance of Notch1 and PTEN on bronchial asthma in children

Objective To investigate the significance of Notch1 and PTEN on bronchial asthma in children.Methods A total of 41 children with bronchial asthma(the study group)and 40 healthy children(the control group)in a hospital in Henan from January 2015 to January 2018 were selected as study objects.Indexes of pulmonary functionforced expiratory volume in one second(FEV 1),FEV 1/forced vital capacity(FVC),middle forced expiratory flow(FEF25%-75%),forced expiratory flow at 50%of FVC(FEF50%),forced expiratory flow at 75%of FVC(FEF75%)and fractional exhaled nitric oxide(FeNO)],interleukin-6(IL-6)and eosinophils(Eos)were detected;expression levels of Notch1 and PTEN mRNA were detected by qRT-PCR;all data were statistically analyzed.Results FEV 1,FEV 1/FVC,FEF25%-75%,FEF50%and FEF75%in the study group were(1.38±0.65)L,(60.35±10.42)%,(3.15±1.23)L/s,(1.76±0.79)L/s and(0.78±0.54)L/s,respectively.All were lower than those in the control group,which were(2.47±0.53)L,(79.46±13.26)%,(4.09±1.57)L/s,(2.57±1.03)L/s and(1.25±0.38)L/s,respectively(all P<0.05).FeNO in the study group was(17.35±11.53)ppb,which was higher than that of(10.46±4.25)ppb in the control group(P<0.05).Eos and IL-6 in the study group were(0.36±0.13)×10^9/L and(0.73±0.17)ng/mL,rspectively.Both were higher than those in the control group,which were(0.16±0.11)×10^9/L and(0.38±0.14)ng/mL,respectively(both P<0.05).Level of Notch1 mRNA in the study group was 1.52±0.13,which was significantly higher than that of 0.87±0.09 in the control group(P<0.05).Level of PTEN mRNA in the study group was 0.38±0.08,which was significantly lower than that of 1.17±0.19 in the control group(P<0.05).The corresponding analysis results showed that expression level of Notch1 mRNA was negatively related with FEV 1,FEV 1/FVC,FEF25%-75%,FEF50%and FEF75%(all P<0.05),and was positively related with FeNO,IL-6 and Eos(all P<0.05).Expression level of PTEN mRNA was positively related with FEV 1,FEV 1/FVC,FEF25%-75%,FEF50%and FEF75%(all P<0.05),and was negatively related with FeNO,IL-6 and Eos(all P<0.05).Expression of Notch1 mRNA was negatively related with expression of PTEN mRNA(P<0.05).Conclusion Upregulation of Notch1 level in children with asthma can suppress the expression of PTEN and promote the expression of inflammation factors like IL-6,so as to induce the development and progression of asthma.