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Biochemical basis of asthma therapy.哮喘治疗的生化基础。
J Biol Chem. 2011 Sep 23;286(38):32899-905. doi: 10.1074/jbc.R110.206466. Epub 2011 Jul 28.
2
Glucocorticosteroids.糖皮质激素
Handb Exp Pharmacol. 2017;237:93-115. doi: 10.1007/164_2016_62.
3
Changing face of β2-adrenergic and muscarinic receptor therapies in asthma.哮喘中β2肾上腺素能受体和毒蕈碱受体疗法的变化趋势
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Asthma: an important disease to otolaryngologists--Part II: Asthma management strategy.哮喘：耳鼻喉科医生的重要疾病——第二部分：哮喘管理策略
Ear Nose Throat J. 1996 Mar;75(3):136-8, 140-2.
5
Molecular mechanisms of antiasthma therapy.抗哮喘治疗的分子机制
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Recent developments in the genetics of asthma.哮喘遗传学的最新进展。
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Combined anti-cholinergic and short-acting β-agonist therapy reduces hospital admissions for acute asthma.联合使用抗胆碱能药物和短效β受体激动剂治疗可减少急性哮喘的住院人数。
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Research and development of bronchodilators for asthma and COPD with a focus on G protein/KCa channel linkage and β2-adrenergic intrinsic efficacy.哮喘和 COPD 支气管扩张剂的研究与开发，重点关注 G 蛋白/KCa 通道的联系和β2 肾上腺素能内在效能。
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本文引用的文献

1
Tiotropium bromide step-up therapy for adults with uncontrolled asthma.噻托溴铵阶梯治疗成人未控制哮喘。
N Engl J Med. 2010 Oct 28;363(18):1715-26. doi: 10.1056/NEJMoa1008770. Epub 2010 Sep 19.
2
QVA149 demonstrates superior bronchodilation compared with indacaterol or placebo in patients with chronic obstructive pulmonary disease.QVA149 相较于茚达特罗或安慰剂，能为慢性阻塞性肺疾病患者带来更优的支气管扩张作用。
Thorax. 2010 Dec;65(12):1086-91. doi: 10.1136/thx.2010.139113. Epub 2010 Oct 26.
3
Eosinophil cysteinyl leukotriene synthesis mediated by exogenous secreted phospholipase A2 group X.外源性分泌型磷脂酶 A2 组 X 介导的嗜酸性粒细胞半胱氨酰白三烯的合成。
J Biol Chem. 2010 Dec 31;285(53):41491-500. doi: 10.1074/jbc.M110.153338. Epub 2010 Oct 25.
4
Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase.他汀类药物通过增加色氨酸 2,3-双加氧酶的诱导，增强哮喘患者吸入皮质类固醇的抗炎作用。
J Allergy Clin Immunol. 2010 Oct;126(4):754-762.e1. doi: 10.1016/j.jaci.2010.08.005.
5
New therapies for asthma: is there any progress?哮喘的新疗法：是否有进展？
Trends Pharmacol Sci. 2010 Jul;31(7):335-43. doi: 10.1016/j.tips.2010.04.009. Epub 2010 Jun 1.
6
Location, location, location: compartmentalization of early events in leukotriene biosynthesis.位置、位置、位置：白三烯生物合成早期事件的分隔。
J Biol Chem. 2010 Aug 13;285(33):25109-14. doi: 10.1074/jbc.R110.125880. Epub 2010 May 27.
7
The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease.罗氟司特的临床前药理学——一种用于慢性阻塞性肺疾病的选择性、口服磷酸二酯酶 4 抑制剂。
Pulm Pharmacol Ther. 2010 Aug;23(4):235-56. doi: 10.1016/j.pupt.2010.03.011. Epub 2010 Apr 7.
8
Targeting phosphoinositide-3-kinase-delta with theophylline reverses corticosteroid insensitivity in chronic obstructive pulmonary disease.茶碱靶向磷酸肌醇 3-激酶 δ 可逆转慢性阻塞性肺疾病中皮质类固醇的不敏感性。
Am J Respir Crit Care Med. 2010 Oct 1;182(7):897-904. doi: 10.1164/rccm.200906-0937OC. Epub 2010 Mar 11.
9
Pharmacological strategies for improving the efficacy and therapeutic ratio of glucocorticoids in inflammatory lung diseases.改善炎症性肺病中糖皮质激素疗效和治疗比率的药理学策略。
Pharmacol Ther. 2010 Feb;125(2):286-327. doi: 10.1016/j.pharmthera.2009.11.003. Epub 2009 Nov 22.
10
Hypoxia-inducible factor 1alpha induces corticosteroid-insensitive inflammation via reduction of histone deacetylase-2 transcription.缺氧诱导因子 1α 通过减少组蛋白去乙酰化酶-2 的转录诱导皮质类固醇不敏感的炎症。
J Biol Chem. 2009 Dec 25;284(52):36047-36054. doi: 10.1074/jbc.M109.025387. Epub 2009 Oct 30.

哮喘治疗的生化基础。

Biochemical basis of asthma therapy.

机构信息

National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom.

出版信息

J Biol Chem. 2011 Sep 23;286(38):32899-905. doi: 10.1074/jbc.R110.206466. Epub 2011 Jul 28.

DOI:10.1074/jbc.R110.206466
PMID:21799015
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3190895/
Abstract

Current therapy for asthma is highly effective. β(2)-Adrenergic receptor (β(2)AR) agonists are the most effective bronchodilators and relax airway smooth muscle cells through increased cAMP concentrations and directly opening large conductance Ca(2+) channels. β(2)AR may also activate alternative signaling pathways that may have detrimental effects in asthma. Glucocorticoids are the most effective anti-inflammatory treatments and switch off multiple activated inflammatory genes through recruitment of histone deacetylase-2, activating anti-inflammatory genes, and through increasing mRNA stability of inflammatory genes. There are beneficial molecular interactions between β(2)AR and glucocorticoid-activated pathways. Understanding these signaling pathways may lead to even more effective therapies in the future.

摘要

目前的哮喘治疗方法非常有效。β（2）-肾上腺素能受体（β（2）AR）激动剂是最有效的支气管扩张剂，通过增加 cAMP 浓度和直接打开大电导钙（2+）通道来松弛气道平滑肌细胞。β（2）AR 也可能激活其他信号通路，这些通路在哮喘中可能有不利影响。糖皮质激素是最有效的抗炎治疗方法，通过招募组蛋白去乙酰化酶-2、激活抗炎基因，以及增加炎症基因的 mRNA 稳定性，从而关闭多个激活的炎症基因。β（2）AR 和糖皮质激素激活途径之间存在有益的分子相互作用。了解这些信号通路可能会导致未来更有效的治疗方法。