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细胞间粘附分子-1(Intercellular adhesion molecule-1,ICAM-1)为介导鼻病毒（Human rhinovirus,HRV）感染支气管哮喘的受体之一，在气道反应性、肺及支气管损伤、炎症因子的调控中发挥关键作用。孟鲁司特钠可缓解气道反应性，减少肺和气管损伤，同时具有抗炎作用。孟鲁司特钠是否可下调ICAM-1从而预防HRV感染引起的支气管哮喘尚不清楚。本研究以BALB/c小鼠为研究对象，随机分为正常对照组、正常给药组、模型对照组和模型给药组（N=30）。模型对照组、模型给药组小鼠构建RV-1B感染支气管哮喘模型，模型给药组给予孟鲁司特钠干预。正常对照组、正常给药组为正常小鼠，正常给药组给与孟鲁司特钠干预。检测各组小鼠肺组织RV-1B拷贝数，测定肺泡灌洗液中免疫球蛋白E(Immunoglobulin E, IgE)、肿瘤坏死因子-α(Tumor necrosis factor-ɑ，TNF-ɑ)、白细胞介素-4(Interferon-4, IL-4)、白细胞介素-13(Interferon-13, IL-13)、半胱氨酰白三烯受体1型抗体（Cysteinyl leukotriene receptor 1 antibody, CysLT1）和γ-干扰素（Interferon-γ,IFN-γ）水平，观察各组小鼠肺组织病理改变，并检测肺组织ICAM-1 mRNA和蛋白的表达水平及嗜酸性粒细胞（Eosinophilic granulocyte, EOS）凋亡水平。结果显示，模型对照组小鼠肺泡间隔及支气管中观察到胶原纤维过度沉积，肺泡腔有红细胞渗出；与模型对照组相比，模型给药组小鼠肺组织胶原纤维沉积明显减少，肺泡腔红细胞渗出减少。模型对照组和模型给药组小鼠肺组织中HRV拷贝数呈先上升后下降的趋势，但两组各时间点的HRV拷贝数无明显差异。与模型对照组相比，模型给药组小鼠肺组织ICAM-1 mRNA和蛋白表达水平明显降低，EOS凋亡指数显著升高。与模型对照组相比，模型给药组肺泡灌洗液IFN-γ水平明显升高，而IgE、TNF-α、IL-4、IL-13和CysLT1水平均明显降低。因此，孟鲁司特钠可下调RV-1B受体靶点ICAM-1的表达，促进EOS凋亡、降低炎症反应，从而减轻RV-1B感染引起的肺组织纤维化。
Abstract：Intercellular adhesion molecule(ICAM)-1 is one of the receptors mediating human rhinovirus(HRV) infection in bronchial asthma(BA). It plays a key part in the regulation of airway reactivity, lung and bronchial injury, and inflammatory factors. Montelukast can alleviate airway reactivity, reduce damage to the lung and trachea, and has anti-inflammatory effects. Whether montelukast sodium(MS) downregulates ICAM-1 expression to prevent BA caused by HRV infection is not known. In this study, BALB/c mice were divided randomly into four groups of 30: normal control, normal treatment, model control, and model treatment. BA models were constructed by RV-1B in the model control group(MCG) and model treatment group(MTG), and mice in the MTG received MS. Mice in the normal control group(NCG) and normal treatment group(NTG) were normal mice, and mice in the NTG received MS. The copy number of RV-1B in the lung tissues of each group of mice was determined. The level of immunoglobulin(Ig)E, tumor necrosis factor(TNF)-α, interleukin(IL)-4, IL-13, cysteinyl leukotriene receptor type 1 antibody(CysLT1) and interferon(IFN)-γ in the bronchoalveolar lavage fluid(BALF) of mice from each group was determined. Pathological changes in each group were observed. Protein and mRNA expression of ICAM-1 as well as the apoptosis level of eosinophils(EOS) in the lung tissues of each group were determined. Excessive deposition of collagen fibers in alveolar septa and bronchus as well as red cells oozing out of the alveolar cavity were observed in the MCG. Compared with the MCG, decreased deposition of collagen fibers in alveolar septa and bronchus as well as fewer red cells oozing out of the alveolar cavity were observed in the MTG. The copy number of RV-1B increased and then decreased in the MCG and MTG, but there was no significant change in the copy number of RV-1B at each time point in either group. Compared with that of the MCG, mRNA and protein expression of ICAM-1decreased obviously and the apoptosis index for EOS increased significantly in the MTG. Compared with that of the MCG, the IFN-γ level in BALF increased, but the level of IgE, TNF-α, IL-4, IL-13 and CysLT1 in BALF decreased in the MTG. Therefore, MS could alleviate the pulmonary fibrosis caused by RV-1B infection by promoting EOS apoptosis and reducing inflammation via downregulating expression of the RV-1B receptor target ICAM-1.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.004542
中图分类号:R562.25
引用信息:
[1]于海英,刘娜.孟鲁司特钠抗鼻病毒RV-1B感染支气管哮喘小鼠模型肺组织纤维化作用的机制研究[J].病毒学报,2024,40(04):687-694.DOI:10.13242/j.cnki.bingduxuebao.004542.
基金信息: