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白三烯受体拮抗剂对哮喘小鼠的气道炎症及肺内一氧化氮合酶的影响 被引量:4

The effect of leukotrine receptor antagonist on murine asthmatic inflammation model and the expression of nitric oxide synthase in the lung
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摘要 目的 :研究白三烯受体拮抗剂对哮喘气道炎症过程及肺内一氧化氮合酶 (NOS)的影响。方法 :C57BL/6J小鼠分为 3组 :哮喘组 (7只 ) ,正常对照组 (6只 ) ,扎鲁司特 (白三烯受体拮抗剂 )组 (7只 )。建立小鼠哮喘模型 ,给予口服扎鲁司特 40mg·kg 1 ·d 1 ,共 5d ,观察支气管肺泡灌洗液 (BALF)中白细胞总数 ,嗜酸细胞百分比 (EOS % ) ,血涂片 ,骨髓片中EOS % ,并用免疫组化的方法观察使用扎鲁司特后诱生型一氧化氮合酶 (iNOS)、内皮型一氧化氮合酶 (eNOS)的表达情况。结果 :哮喘组BALF中白细胞总数 [(1 3 .9± 0 .8)× 1 0 6 ml 1 ]、EOS % [(47.75± 1 3 .0 9) % ]显著高于正常对照组 (P <0 .0 0 1 ) ,正常对照组相应数值分别为 (1 .9± 0 .5)× 1 0 6 ml 1 和 (0 .2± 0 .0 1 ) % ,口服扎鲁司特后BALF中白细胞总数 [(1 .3± 0 .4)× 1 0 6 ml 1 ]、EOS % [(1 .33± 1 .0 7) % ]显著低于哮喘组 (P <0 .0 0 1 ) ,哮喘组激发后第一天血涂片中EOS % [(1 8.75± 8.54) % ]显著高于对照组 [(1 .5± 1 .0 ) % ,P <0 .0 0 1 ] ,扎鲁司特组在激发后第 1天血涂片中EOS %则较正常对照组明显下降 [(6 .95± 3 .83) % ] ,哮喘组骨髓片中EOS % [(1 3 .5±3 .9) % ]显著高于正常对照组 [(2 .5± 2 .9) % ] ,而扎鲁司特组 [( Objective:To investigate the role of Zafirlukast, a selective leukotriene D 4 receptor antagonist in treatment of asthmatic inflammation and its effect in the expression of nitric oxide synthase (NOS) in lungs. Methods:A murine model was set up(asthma model group,control mice group ),then the number of WBC,eosinophils %(EOS%) in bronchoalveolar lavage fluid (BALF),eosinophils% (EOS%) in blood and bone marrow were measured after treatment with Zafrilukast. The expression of inducible nitric oxide synthase (iNOS) and of endothelium nitric oxide synthase (eNOS) were studied by immunohistochemistry. Results:There was a significant increase in number in WBC [(13.9±0.8)×10 6 ml 1 vs (1.9±0.5) ×10 6 ml 1 , P <0.001], EOS%[(47.75± 13.09)% vs (0.2±0.01)%, P <0.001] in BALF after antigen challenge.There was also a significant increase in EOS% of the first day after challenge in blood[(18.75±8.54)% vs (1.5±1.0)%, P <0.001] and EOS% in bone marrow[(13.5±3.9)% vs (2.5±2.9)%, P <0.001].After administration of Zafrilukast the number of WBC [ (1.3±0.4)×10 6/ml, P <0.001], EOS% [ (1.33± 1.07)%, P <0.001], EOS% of the first day after challenge in blood [(6.95±3.83)%, P <0.001]were significantly decreased. But there was no significant reduction in bone marrow after management with Zafrilukast .There was a significant reduction of iNOS expression , but no siginificant change in eNOS expression after treatment with Zafrilukast. Conclusion: EOS in asthmatic inflammation originate from the margin pool of blood and the bone marrow. Zafrilukast can inhibit EOS infiltration in asthmatic inflammation, and can also inbibit iNOS expression in lungs directly or indirectly.
出处 《北京大学学报(医学版)》 CAS CSCD 北大核心 2002年第1期52-56,共5页 Journal of Peking University:Health Sciences
关键词 哮喘 哮酸细胞 药物作用 扎鲁司特 一氧化氮合酶 气管炎 药物疗法 实验研究 白三烯 Asthma Eosinophils/drug eff Zafrilukast Nitric oxide synthase Trachitis/drug ther Receptors,leukotriene/antag
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参考文献10

  • 1[1]Hessel EM,Van Oosterhout AJM,Hofstra CL,et al.Bronchoconstriction and airway responsiveness after ovalbumin inhalation in sensitized mice[J]. Eur J Pharmacol, 1995,293 :401-412
  • 2[2]Kung TT,Jones H,Adams Ⅲ GK,et al.Characterization of a murine model of allergic pulmonary inflammation [J]. Int Arch Allergy Immunol,1994,105: 83-90
  • 3[3]Gawchik SM, Saccar CL. Role of antileukotriene agents in asthma therapy[J]. J Am Osteopath Assoc, 2000, 100(1):37-43
  • 4[4]O'Byrne PM. Leukotrienes in the pathogenesis of asthma[J]. Chest,1997,2 (Suppl):27-34
  • 5[5]Kemp JP. Zafirlukast,a selective leukotriene D4 receptor antagonist: a new class of therapy for patients with asthma[J] . Therapy Trends, 1996,14:89-102
  • 6[6]Smith LJ, Glass M, Minkwitz MC. Inhibiton of leukotriene D4-inducecl bronchoconstriction in subjects with asthma:a concentration-effect study of ICI 204,219[J].Clin Pharmacol Ther,1993,54(4):430-436
  • 7[7]Calhoun WJ, Lavins B J,Minkwits MC, et al. Effect of Zafrilukast (Accolate) on cellular mediator of inflammation: Bronchoalveolar lavage fluid findings after segmetal antigen challenge[J]. Am J Respir Crit Care Med ,1998, 157(5pt1):1381-1389
  • 8[8]Pearlman DS, Ostrom NK, Bronsky EA, et al. The leukotriene D4-receptor antagonist zafirlukast attenuates exercise-induced bronchoconstriction in children[J]. J Pediatr ,1999 ,134(3):273-279
  • 9[9]Kung TT,Jones H, AdamsⅢ GK,et al. Characterization of a murine model of allergic pulmonary inflammation[J]. Int Arch Allergy Immunol , 1994, 105:83-90
  • 10[10]Kharitonov SA, Yates DH, Barnes PJ. Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients[J]. Am J Respir Crit Care Med, 1996,153:454-457

同被引文献34

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  • 2李志敏,王伟群.孟鲁司特治疗小儿支气管哮喘疗效观察[J].儿科药学杂志,2004,10(3):36-37. 被引量:18
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  • 4儿童阻塞性睡眠呼吸暂停低通气综合征诊疗指南草案(乌鲁木齐)[J].中华耳鼻咽喉头颈外科杂志,2007,42(2):83-84. 被引量:643
  • 5[1]CARRIE A R,MERYL H K. Diisocyanate asthma:clinical aspects and immunopathogenesis[J]. International immunopharmacology,2002(2):213-215.
  • 6[2]WALSH G M. Eosinophileapoptosis:Mechanisms and clinical relevance in asthmatic and allergic inflammation[J]. BrJHaetol,2000,111:61-63.
  • 7Tamaoki J, Kondo M, Sakai N, et al. Leukotriene antagonist prevents exacerbarion of asthma during reduction of high-dose inhaled corticosteroid [J]. Am J Resoir Carit Cave Med,1997, 155: 1235.
  • 8Minoguchi K, Kohno Y, Minoguchi H, et al. Reduction of eosinophilic inflammation in the airways of patients with asthma using montelukast [J]. Chest, 2002, 121: 732.
  • 9Stelmaeh I, Jerzynska J, Kuna P. A randomized, double-blind trial of the effect of treatment with montelukast on bronchial hyperresponsiveness and serum eosinophilic cationic protein (ECP), soluble interleukin 2 receptor (SIL-2R), IL-4, snd soluble intercellular adhesion molecule 1 (sICAM-1) in children with asthma [J]. J Allergy Clin Immunol, 2002, 109: 257.
  • 10Van den Toorn LM, Overbeek SE, de Jongste JC, et al. Airway inflmation is present during clinical remission of atopic asthma [J]. Am J Respir Crit Care Med, 2001, 164: 2107.

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