【摘要】 目的 研究维生素D₃辅助糖皮质激素对小儿支气管哮喘Toll样受体4（TLR4）/核因子κB（NF-κB）信号通路相关因子水平的影响。方法 选取2019年1月—2022年1月长江大学附属荆州医院收治的120例小儿支气管哮喘患儿作为研究对象，按照随机数表法将患儿分为A组、B组和C组，每组40例。所有患儿给予常规治疗，C组在常规治疗基础上给予安慰剂，B组在常规治疗基础上给予糖皮质激素，A组在B组基础上给予维生素D₃。观察各组患儿喘息、胸闷、气促及咳嗽症状持续时间，分析各组患儿治疗前后TLR4和NF-κB mRNA表达，并比较3组治疗前后气道炎症指标[嗜酸性粒细胞（EOS）、白细胞介素-4（IL-4）、肿瘤坏死因子α（TNF-α）、C反应蛋白（CRP）]水平，比较各组患儿治疗前后肺功能[第1秒用力呼气容积占预计值百分比（FEV1%pred）、用力肺活量（FVC）、每秒呼气峰流速（PEF）及FEV1/FVC值]。结果 A组喘息、胸闷、气促及咳嗽症状持续时间短于B组和C组（P <0.05）,B组短于C组（P <0.05）。A组治疗前后TLR4和NF-κB mRNA相对表达量的差值高于B组和C组（P <0.05）,B组高于C组（P <0.05）。A组治疗前后IL-4、EOS、TNF-α、CRP的差值高于B组和C组（P <0.05）,B组高于C组（P <0.05）。A组治疗前后FEV1%pred、FVC、FEV1/FVC、PEF的差值高于B组和C组（P <0.05）,B组高于C组（P <0.05）。Pearson相关性分析显示，IL-4、EOS、TNF-α、CRP水平与TLR4 mRNA呈正相关（r=0.501、0.574、0.462和0.474，均P <0.05），与NF-κB mRNA呈正相关（r=0.496、0.522、0.485和0.492，均P <0.05）。FEV1%pred、FVC、FEV1/FVC、PEF水平与TLR4 mRNA呈负相关（r=-0.596、-0.542、-0.513和-0.505，均P<0.05），与NF-κB mRNA呈负相关（r=-0.561、-0.505、-0.526和-0.518，均P <0.05）。结论 维生素D₃辅助糖皮质激素治疗小儿支气管哮喘可通过调控TLR4/NF-κB信号通路，减轻患儿气道炎症反应，并有效提升肺功能，具有良好的临床应用价值。更多还原

【Abstract】 Objective To investigate the effects of vitamin D₃ and glucocorticoid on levels of factors associated with the Toll-like receptor 4（TLR4）/nuclear factor-kappa B（NF-κB） signaling pathway in children with bronchial asthma. Methods From January 2019 to January 2022, a total of 120 cases of children with bronchial asthma admitted in our hospital were selected and divided into group A, B and C with the random number table, with 40 cases in each group. All patients were given conventional treatment, on the basis of which those in the group C and group B were administrated with placebo and glucocorticoids, respectively. Besides, patients in the group A were additionally treated with both glucocorticoids and vitamin D₃. The duration of symptoms including wheezing, chest tightness, shortness of breath and cough was observed among children in the three groups. The mRNA expressions of TLR4 and NF-κB, the levels of indicators related to the airway inflammation [eosinophil（EOS） count and levels of interleukin-4（IL-4）, tumor necrosis factor-α（TNF-α） and C-reactive protein（CRP）], and the pulmonary function [forced expiratory volume in one second（FEV1） percentage predicted（FEV1%pred）, forced vital capacity（FVC）,peak expiratory flow（PEF） and FEV1/FVC] before and after the treatment were analyzed and compared among the groups. Results The duration of wheezing, chest tightness, shortness of breath and cough in group A was shorter than that in group B and C, while that in group B was even shorter than that in group C（P < 0.05）. The differences of m RNA expressions of TLR4 and NF-κB before and after the treatment in group A were higher than those in groups B and C, and those in group B were higher relative to those in group C（P < 0.05）. The differences of the levels of IL-4,TNF-α and CRP as well as the EOS count before and after the treatment in group A were higher than those in groups B and C, and those in group B were higher than those in group C（P < 0.05）. The differences of FEV1%pred, FVC,FEV1/FVC and PEF before and after the treatment in group A were higher than those in group B and C, and those in group B were even higher than those in group C（P < 0.05）. Pearson correlation analysis showed that the mRNA level of TLR4 was positively correlated with levels of IL-4, EOS, TNF-α and CRP（r =0.501, 0.574, 0.462 and 0.474, all P < 0.05）, and the mRNA level of NF-κB was also positively correlated with levels of IL-4, EOS, TNF-αand CRP（r =0.496, 0.522, 0.485 and 0.492, all P <0.05）. In addition, both mRNA levels of TLR4 and NF-κB were negatively correlated with FEV1%pred, FVC, FEV1/FVC and PEF（for TLR4: r =-0.596,-0.542,-0.513 and-0.505,all P <0.05; for NF-κB: r =-0.561,-0.505,-0.526 and-0.518, all P <0.05）. Conclusions Treatment with vitamin D₃and glucocorticoid could alleviate airway inflammation and effectively improve the pulmonary function by regulating the TLR4/NF-κB signaling pathway in children with bronchial asthma, and is of great clinical value.更多还原