黑龙江省森工总医院(黑龙江省红十字医院)呼吸科;黑龙江省森工总医院(黑龙江省红十字医院)消化科;
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。
| 138 | 0 | 180 |
| 下载次数 | 被引频次 | 阅读次数 |
[2] Chowdhury NU, Guntur VP, Newcomb DC, et al. Sex and gender in asthma[J]. Eur Respir Rev, 2021, 30(162):210067. DOI:10. 1183/16000617. 0067-2021.
[3] Capilupi MJ, Kerath SM, Becker LB. Vagus nerve stimulation and the cardiovascular system[J]. Cold Spring Harb Perspect Med, 2020, 10(2):a034173.DOI:10. 1101/cshperspect. a034173.
[4] Michi AN, Love ME, Proud D. Rhinovirus-induced modulation of epithelial phenotype:role in asthma[J].Viruses, 2020, 12(11):E1328. DOI:10. 3390/v12111328.
[5] Cha?ubiński M, Gajewski A, Kowalski ML. The relationship between human coronaviruses, asthma and allergy-An unresolved dilemma[J]. Clin Exp Allergy,2020, 50(10):1122-1126. DOI:10. 1111/cea. 13718.
[6] Petat H, Gajdos V, Angoulvant F, et al. High frequency of viral co-detections in acute bronchiolitis[J].Viruses, 2021, 13(6):990. DOI:10. 3390/v13060990.
[7] Nakamura M, Shimizu T. Recent advances in function and structure of two leukotriene B4 receptors:BLT1and BLT2[J]. Biochem Pharmacol, 2022, 203:115178. DOI:10. 1016/j. bcp. 2022. 115178.
[8] Bartlett NW, Walton RP, Edwards MR, et al. Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation[J]. Nat Med, 2008, 14:199-204. DOI:10. 1038/nm1713.
[9]谢慎昕，黄顺开，秦旭，等.鼻病毒感染小鼠支气管哮喘模型的建立[J].中华结核和呼吸杂志，2019, 42(4):294-296. DOI:10. 3760/cma. j. issn. 1001-0939. 2019. 04. 012.
[10]Richard HL，郑月华.实验动物的药物剂量[J].实验动物与比较医学，1984,4(3):178-182.
[11]Ortega H, Nickle D, Carter L. Rhinovirus and asthma:Challenges and opportunities[J]. Rev Med Virol,2021, 31(4):e2193. DOI:10. 1002/rmv. 2193.
[12]Shukla SD, Shastri MD, Vanka SK, et al. Targeting intercellular adhesion molecule-1(ICAM-1)to reduce rhinovirus-induced acute exacerbations in chronic respiratory diseases[J]. Inflammopharmacology, 2022,30(3):725-735. DOI:10. 1007/s10787-022-00968-2.
[13]Tang XY, Chen PB, Du DJ, et al. Acupoint catgut embedment may reduce airway inflammation reaction by down-regulating ICAM-1 and EOS by suppressing p38MAPK signaling in lung tissue of asthmatic rats[J].Zhen Ci Yan Jiu, 2022, 47(2):129-134. DOI:10. 13702/j. 1000-0607. 201279.
[14]Liu Y, Bochkov YA, Eickhoff JC, et al. Orosomucoidlike 3 supports rhinovirus replication in human epithelial cells[J]. Am J Respir Cell Mol Biol, 2020, 62(6):783-792. DOI:10. 1165/rcmb. 2019-0237oc.
[15]Yamaya M, Nomura K, Arakawa K, et al.Clarithromycin decreases rhinovirus replication and cytokine production in nasal epithelial cells from subjects with bronchial asthma:effects on IL-6, IL-8 and IL-33[J]. Arch Pharmacal Res, 2020, 43(5):526-539.DOI:10. 1007/s12272-017-0950-x.
[16]Pazderova P, Waltl EE, Niederberger-Leppin V, et al.ELISA-based assay for studying major and minor group rhinovirus-receptor interactions[J]. Vaccines(Basel),2020, 8(2):E315. DOI:10. 3390/vaccines8020315.
[17]Liou CJ, Chen YL, Yu MC, et al. Sesamol alleviates airway hyperresponsiveness and oxidative stress in asthmatic mice[J]. Antioxidants(Basel), 2020, 9(4):E295. DOI:10. 3390/antiox9040295.
[18]Mehta AK, Croft M. Rhinovirus infection promotes eosinophilic airway inflammation after prior exposure to house dust mite allergen[J]. Immunohorizons, 2020, 4(8):498-507. DOI:10. 4049/immunohorizons. 2000052.
[19]Ko YK, Zhang YL, Wee JH, et al. Human rhinovirus infection enhances the Th2 environment in allergic and non-allergic patients with chronic rhinosinusitis[J]. Clin Exp Otorhinolaryngol, 2021, 14(2):217-224. DOI:10. 21053/ceo. 2020. 00444.
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: