维生素D3辅助糖皮质激素对小儿支气管哮喘TLR4/NF-κB信号通路相关因子水平的影响

Effects of vitamin D3 and glucocorticoid on levels of factors associated with the TLR4/NF-κB signaling pathway in children with bronchial asthma

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。

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 mRNA 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-α and 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 D₃ and 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.