组蛋白脱乙酰酶及其在哮喘中的作用
2012/02/29
目的:本研究旨在对经典的组蛋白脱乙酰酶(HDAC)和HDAC抑制剂进行概述,并针对其中某些化合物的潜在抗哮喘作用进行讨论。
方法:对Medline数据库进行检索,检索主题词为“哮喘和HDAC”、“哮喘和曲古菌素A”、“过敏性气道疾病和曲古菌素A”以及“过敏性气道疾病和丙戊酸”。检索过去10年文献。对1960年代后的文献检索,获取有关抗癫痫药治疗哮喘的信息。
结果:有关抗癫痫药物(如HDAC抑制剂、丙戊酸)初步临床试验显示,这些药物具有长期的抗哮喘作用。HDAC抑制剂原型(曲古菌素A)治疗鼠过敏性气道疾病的研究显示,该药也有助于哮喘的治疗。
结论:虽然有关HDAC的抗哮喘具体机制尚存在争议,但抑制气道高反应性、抑制气道收缩和抗炎作用可能参与了HDAC抑制剂的抗哮喘机制。
(林江涛 审校)
J Asthma. 2012 Jan 10. [Epub ahead of print]
Histone Deacetylases and Their Role in Asthma.
Royce SG, Karagiannis TC.
Source
Allergy and Immune Disorders, Murdoch Children’s Research Institute , Parkville, VIC , Australia.
Abstract
OBJECTIVE:The aim of this article is to provide an overview of the classical histone deacetylase (HDAC) enzymes and HDAC inhibitors. The discussion is focused on the potential anti-asthmatic effects of this group of compounds.
METHODS:Medline was used with the search terms, "asthma and HDAC," "asthma and Trichostatin A," "asthma and valproic acid," "allergic airways disease and HDAC," "allergic airways disease and Trichostatin A," and "allergic airways disease and valproic acid." Manuscripts from the past decade were accessed. Historical literature dating from the 1960s was accessed for the use of anti-epileptics in the treatment of asthma.
RESULTS:Preliminary clinical trials with anti-epileptic drugs including the well-known HDAC inhibitor, valproic acid, have shown long-lasting anti-asthmatic effects providing the basis for the evaluation of this class of compounds in asthma. Studies using the prototypical HDAC inhibitor, Trichostatin A, in well-established murine models of allergic airways disease have also indicated beneficial effects.
CONCLUSION:Although the precise mechanisms are still controversial, inhibition of airway hyperresponsiveness and agonist-induced contraction as well as anti-inflammatory effects have been described for HDAC inhibitors in asthma.
J Asthma. 2012 Jan 10. [Epub ahead of print]
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有和无阿司匹林过敏的哮喘患者,支气管阿司匹林激发试验中呼出气类花生酸类物质含量:初步研究
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哮喘活动病程:人群研究