切换至 "中华医学电子期刊资源库"

中华妇幼临床医学杂志(电子版) ›› 2017, Vol. 13 ›› Issue (02) : 234 -239. doi: 10.3877/cma.j.issn.1673-5250.2017.02.022

所属专题: 文献

综述

白三烯及其受体拮抗剂在肺部疾病中作用的研究进展
吴华1   
  1. 1. 210029 南京医科大学第一附属医院儿科
  • 收稿日期:2016-11-17 修回日期:2017-02-07 出版日期:2017-04-01

Research progress of leukotrienes and leukotriene receptor antagonists in pulmonary diseases

Hua Wu1   

  1. 1. Department of Pediatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
  • Received:2016-11-17 Revised:2017-02-07 Published:2017-04-01
  • About author:
    Corresponding author: Chen Xiaoqing, Email:
引用本文:

吴华. 白三烯及其受体拮抗剂在肺部疾病中作用的研究进展[J]. 中华妇幼临床医学杂志(电子版), 2017, 13(02): 234-239.

Hua Wu. Research progress of leukotrienes and leukotriene receptor antagonists in pulmonary diseases[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2017, 13(02): 234-239.

白三烯是花生四烯酸经5-脂氧合酶代谢途径形成的具有高度生物活性的代谢产物,是重要的炎症介质。研究结果表明,白三烯参与了支气管哮喘、慢性阻塞性肺疾病(COPD)、毛细支气管炎、支气管肺发育不良(BPD)及急性肺损伤(ALI)等多种肺部疾病的病理生理过程。白三烯通过与靶细胞膜上的受体结合而发挥致炎作用,故白三烯受体拮抗剂(LTRA)可通过与白三烯受体竞争性结合而起到抗炎作用,在改善肺功能、降低气道高反应性、抑制气道重塑及抗肺纤维化中发挥重要作用。近年研究结果显示,LTRA还具有重要的非受体依赖性抗炎作用。笔者拟就白三烯和LTRA在肺部疾病中作用的研究进展进行综述,为肺部疾病的治疗提供新思路。

Leukotrienes are important inflammatory mediators derived from arachidonic acid through the 5-lipoxygenase pathway. Leukotrienes are implicated in the pathogenesis of many kinds of pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD), bronchiolitis, bronchopulmonary dysplasia (BPD) and acute lung injury (ALI), etc.. Leukotrienes exert multiple biological effects by binding to cognate cell-surface receptors and leukotriene receptor antagonists (LTRA) produce their anti-inflammatory effects by competitively combining with leukotriene receptors, playing an important role in improving pulmonary function, decreasing airway hyperresponsiveness, inhibiting airway remodeling and pulmonary fibrosis. Anti-inflammatory activities of LTRA independent of leukotriene receptors have recently been suggested in recent researches. This review discusses the research progress of leukotrienes and the application of LTRA in pulmonary diseases, thus providing new ways for the treatment of pulmonary diseases.

图1 白三烯的生物合成途径
[1]
Peters-Golden M, Henderson WR Jr. Leukotrienes[J]. N Engl J Med, 2007, 357(18): 1841-1854.
[2]
Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary[J]. Eur Respir J, 2008, 31(1): 143-178.
[3]
Rabinovitch N. Urinary leukotriene E4 as a biomarker of exposure, susceptibility and risk in asthma[J]. Immunol Allergy Clin North Am, 2012, 32(3): 433-445.
[4]
Peters-Golden M, Sampson AP. Cysteinyl leukotriene interactions with other mediators and with glucocorticosteroids during airway inflammation[J]. J Allergy Clin Immunol, 2003, 111(Suppl 1): S37-S42; discussion S43-S48.
[5]
Liu M, Yokomizo T. The role of leukotrienes in allergic diseases[J]. Allergol Int, 2015, 64(1): 17-26.
[6]
Woszczek G, Chen LY, Alsaaty S, et al. Concentration-dependent noncysteinyl leukotriene type 1 receptor-mediated inhibitory activity of leukotriene receptor antagonists[J]. J Immunol, 2010, 184(4): 2219-2225.
[7]
Anderson R, Theron AJ, Gravett CM, et al. Montelukast inhibits neutrophil pro-inflammatory activity by a cyclic AMP-dependent mechanism[J]. Br J Pharmacol, 2009, 156(1): 105-115.
[8]
中华医学会儿科学分会呼吸学组. 白三烯受体拮抗剂在儿童常见呼吸系统疾病中的临床应用专家共识[J]. 中华实用儿科临床杂志, 2016, 31(13):973-977.
[9]
Bisgaard H, Skoner D, Boza ML, et al. Safety and tolerability of montelukast in placebo-controlled pediatric studies and their open-label extensions[J]. Pediatr Pulmonol, 2009, 44(6): 568-579.
[10]
Sarkar M, Koren G, Kalra S, et al. Montelukast use during pregnancy: a multicentre, prospective, comparative study of infant outcomes[J]. Eur J Clin Pharmacol, 2009, 65(12): 1259-1264.
[11]
Chan AL, Juarez MM, Gidwani N, et al. Management of critical asthma syndrome during pregnancy[J]. Clin Rev Allergy Immunol, 2015, 48(1): 45-53.
[12]
Lim A, Stewart K, König K, et al. Systematic review of the safety of regular preventive asthma medications during pregnancy[J]. Ann Pharmacother, 2011, 45(7-8): 931-945.
[13]
Hung CH. Role of leukotriene receptor antagonists in asthma[J]. Pediatr Neonatol, 2012, 53(4): 219-220.
[14]
Bérubé D, Djandji M, Sampalis JS, et al. Effectiveness of montelukast administered as monotherapy or in combination with inhaled corticosteroid in pediatric patients with uncontrolled asthma: a prospective cohort study[J]. Allergy Asthma Clin Immunol, 2014, 10(1): 21.
[15]
Kuo CH, Yang SN, Kuo HF, et al. Cysteinyl leukotriene receptor antagonist epigenetically modulates cytokine expression and maturation of human myeloid dendritic cells[J]. Pulm Pharmacol Ther, 2016, 39: 28-37.
[16]
Tsai MJ, Wu PH, Sheu CC, et al. Cysteinyl leukotriene receptor antagonists decrease cancer risk in asthma patients[J]. Sci Rep, 2016, 6: 23979.
[17]
中华医学会儿科学分会呼吸学组. 儿童支气管哮喘诊断与防治指南(2016年版)[J]. 中华儿科杂志,2016, 54(3): 167-181.
[18]
陈秋芳, 张海邻, 余刚, 等. 呼吸道合胞病毒毛细支气管炎患儿炎症递质的变化[J].临床儿科杂志, 2014, 32(2): 115-117.
[19]
Oh JW, Shin SA, Lee HB. Urine leukotriene E and eosinophil cationic protein in nasopharyngeal aspiration from young wheezy children[J]. Pediatr Allergy Immunol, 2005, 16(5): 416-421.
[20]
李洁, 潘家华. 孟鲁司特对毛细支气管炎患儿白三烯水平的影响[J]. 中国当代儿科杂志, 2015, 17(10): 1062-1065.
[21]
Kearns GL, Lu S, Maganti L, et al. Pharmacokinetics and safety of montelukast oral granules in children 1 to 3 months of age with bronchiolitis[J]. J Clin Pharmacol, 2008, 48(4): 502-511.
[22]
Lopez-Campos JL, Calero-Acuña C, Lopez-Ramirez C, et al. Implications of the inflammatory response for the identification of biomarkers of chronic obstructive pulmonary disease[J]. Biomark Med, 2016, 10(2): 109-122.
[23]
Tufvesson E, Ekberg M, Bjermer L. Inflammatory biomarkers in sputum predict COPD exacerbations[J]. Lung, 2013, 191(4): 413-416.
[24]
Rubinstein I, Kumar B, Schriever C. Long-term montelukast therapy in moderate to severe COPD: a preliminary observation[J]. Respir Med, 2004, 98(2): 134-138.
[25]
雷震, 左莹. 孟鲁司特治疗慢性阻塞性肺疾病急性加重期80例疗效分析[J]. 实用药物与临床,2012,15(6): 342-343.
[26]
Abdel Kawy HS. Montelukast versus dexamethasone treatment in a guinea pig model of chronic pulmonary neutrophilic inflammation[J]. COPD, 2016, 13(4): 455-463.
[27]
Lee JH, Kim HJ, Kim YH. The effectiveness of anti-leukotriene agents in patients with COPD: a systemic review with Meta-analysis[J]. Lung, 2015, 193(4): 477-486.
[28]
Shahzad T, Radajewski S, Chao CM, et al. Pathogenesis of bronchopulmonary dysplasia: when inflammation meets organ development[J]. Mol Cell Pediatr, 2016, 3(1): 23.
[29]
Peters-Golden M, Gleason MM, Togias A. Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitis[J]. Clin Exp Allergy, 2006, 36(6): 689-703.
[30]
金蕊, 卢红艳, 罗妍妍, 等. 尿半胱氨酸白三烯E4诊断支气管肺发育不良的临床评价[J]. 中华儿科杂志, 2016, 54(9): 703-707.
[31]
Peters-Golden M, Gleason MM, Togias A. Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitis[J]. Clin Exp Allergy, 2006, 36(6): 689-703.
[32]
Rupprecht T, Rupprecht C, Harms D, et al. Leukotriene receptor blockade as a life-saving treatment in severe bronchopulmonary dysplasia[J]. Respiration, 2014, 88(4): 285-290.
[33]
Kim SB, Lee JH, Lee J, et al. The efficacy and safety of montelukast sodium in the prevention of bronchopulmonary dysplasia[J]. Korean J Pediatr, 2015, 58(9): 347-353.
[34]
Auner B, Geiger EV, Henrich D, et al. Circulating leukotriene B4 identifies respiratory complications after trauma[J]. Mediators Inflamm, 2012, 2012: 536156.
[35]
刘涛, 任成山. 炎症介质在急性肺损伤/急性呼吸窘迫综合征发病机制中的作用[J/CD]. 中华肺部疾病杂志(电子版), 2013, 6(3): 60-63,70.
[36]
Reiss LK, Uhlig U, Uhlig S. Models and mechanisms of acute lung injury caused by direct insults[J]. Eur J Cell Biol, 2012, 91(6-7): 590-601.
[37]
Bhatia M, Moochhala S. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome[J]. J Pathol, 2004, 202(2): 145-156.
[38]
Bitencourt CS, Bessi VL, Huynh DN, et al. Cooperative role of endogenous leucotrienes and platelet-activating factor in ischaemia-reperfusion-mediated tissue injury[J]. J Cell Mol Med, 2013, 17(12): 1554-1565.
[39]
Tsubomatsu C, Shintani T, Abe A, et al. Diagnosis and treatment of obstructive sleep apnea syndrome in children[J]. Adv Otorhinolaryngol, 2016, 77: 105-111.
[40]
Tsaoussoglou M, Lianou L, Maragozidis P, et al. Cysteinyl leukotriene receptors in tonsillar B- and T-lymphocytes from children with obstructive sleep apnea[J]. Sleep Med, 2012, 13(7): 879-885.
[41]
Shen Y, Xu Z, Huang Z, et al. Increased cysteinyl leukotriene concentration and receptor expression in tonsillar tissues of Chinese children with sleep-disordered breathing[J]. Int Immunopharmacol, 2012, 13(4): 371-376.
[42]
梁敏, 朱美华, 王志坚, 等. 白三烯B4与儿童腺样体肥大的关系研究[J]. 中国妇幼保健, 2015, 30(17):2765-2767.
[43]
Shokouhi F, Meymaneh Jahromi A, Majidi MR, et al. Montelukast in adenoid hypertrophy: its effect on size and symptoms[J]. Iran J Otorhinolaryngol, 2015, 27(83): 443-448.
[44]
Goldbart AD, Greenberg-Dotan S, Tal A. Montelukast for children with obstructive sleep apnea: a double-blind, placebo-controlled study[J]. Pediatrics, 2012, 130(3): e575-e580.
[45]
Kheirandish L, Goldbart AD, Gozal D. Intranasal steroids and oral leukotriene modifier therapy in residual sleep-disordered breathing after tonsillectomy and adenoidectomy in children[J]. Pediatrics, 2006, 117(1): e61-e66.
[46]
宁静, 徐勇胜, 董汉权. 孟鲁司特治疗肺炎支原体感染临床效果及对白三烯水平的影响[J].中华医院感染学杂志, 2014, 24(6):1375-1377.
[47]
鞠善良, 李超, 王在义. N-乙酰半胱氨酸联合小剂量糖皮质激素治疗特发性肺间质纤维化疗效的Meta分析[J]. 中国循证医学杂志, 2013, 13(6):717-722.
[1] 韩圣瑾, 周正武, 翁云龙, 黄鑫. 碳酸氢钠林格液联合连续性肾脏替代疗法对创伤合并急性肾损伤患者炎症水平及肾功能的影响[J]. 中华危重症医学杂志(电子版), 2023, 16(05): 376-381.
[2] 陈大敏, 曹晓刚, 曹能琦. 肥胖对胃癌患者手术治疗效果的影响研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 651-653.
[3] 贾成朋, 王代宏, 陈华, 孙备. 可切除性胰腺癌预后术前预测模型的建立及应用[J]. 中华普外科手术学杂志(电子版), 2023, 17(05): 566-570.
[4] 伍学成, 李远伟, 袁武雄, 王建松, 石泳中, 卢强, 李卓, 陈佳, 刘哲, 滕伊漓, 高智勇. 炎症介质谱联合降钙素原在尿源性脓毒血症中的诊断价值[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 476-480.
[5] 王可, 范彬, 李多富, 刘奎. 两种疝囊残端处理方法在经腹腹膜前腹股沟疝修补术中的疗效比较[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 692-696.
[6] 熊欢庆, 李玉娟, 陈键, 刘刚, 李志超, 金发光. 丹参酮IIA及苦参碱组方对脂多糖致小鼠急性肺损伤的协同保护作用[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 455-459.
[7] 唐英俊, 李华娟, 王赛妮, 徐旺, 刘峰, 李羲, 郝新宝, 黄华萍. 人脐带间充质干细胞治疗COPD小鼠及机制分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 476-480.
[8] 徐丽玲, 卢玉宝, 赵彦, 任利, 李姝艺, 符娟, 康玲, 汪青松, 尤再春. COPD管理云平台的构建及临床应用[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 481-484.
[9] 李海明, 刘鸿飞, 李俊. 血清脂蛋白酶水平与COPD患者骨骼肌质量减少的关系[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 500-503.
[10] 邹勇, 顾应江, 丁昊, 杨呈浩, 陈岷辉, 蔡昱. 基于Nrf2/HO-1及NF-κB信号通路探讨葛根素对大鼠脑出血后早期炎症反应及氧化应激反应的影响[J]. 中华脑科疾病与康复杂志(电子版), 2023, 13(05): 271-277.
[11] 屈霄, 王靓, 陆萍, 何斌, 孙敏. 外周血炎症因子及肠道菌群特征与活动性溃疡性结肠炎患者病情的相关性分析[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 466-470.
[12] 朱风尚, 舍玲, 丁永年, 杨长青. 警惕炎症性肠病与少见肠道疾病的鉴别诊断[J]. 中华消化病与影像杂志(电子版), 2023, 13(05): 273-276.
[13] 周婷, 孙培培, 张二明, 安欣华, 向平超. 北京市石景山区40岁及以上居民慢性阻塞性肺疾病诊断现状调查[J]. 中华临床医师杂志(电子版), 2023, 17(07): 790-797.
[14] 孙培培, 张二明, 时延伟, 赵春燕, 宋萍萍, 张硕, 张克, 周玉娇, 赵璨, 闫维, 吴蓉菊, 宋丽萍, 郭伟安, 马石头, 安欣华, 包曹歆, 向平超. 北京市石景山区40岁及以上居民慢性阻塞性肺疾病患病情况及相关危险因素分析[J]. 中华临床医师杂志(电子版), 2023, 17(06): 711-719.
[15] 刘感哲, 艾芬. MiRNA-210通过抑制HIF-1α的表达改善大鼠血管性认知功能障碍[J]. 中华脑血管病杂志(电子版), 2023, 17(05): 489-494.
阅读次数
全文


摘要