TRPV4通道阻滞剂对实验性过敏性哮喘模型气道炎症和气道防御反射的影响

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Jozef Mažerik , Eduard Gondáš , Lukáš Smieško , Soňa Fraňová , Martina Šutovská
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引用次数: 0

摘要

瞬时受体电位(TRP)通道调节生理和病理过程。其活性和敏感性的变化可能与哮喘的病理生理学有关。本研究调查了吸入TRPV4通道阻断剂HC-067047在卵清蛋白诱导的过敏性哮喘实验豚鼠模型中的作用。我们监测了50nM、100nM和150nM HC-067047浓度对体内气道防御反射和体外气管平滑肌收缩性的影响。通过分析来自肺匀浆的慢性炎症标志物来研究HC-067047的抗炎作用。结果表明,HC-067047在体内可抑制气道防御反射,在体外可抑制乙酰胆碱诱导的收缩性。免疫学分析显示,TRPV4通道阻断导致炎性细胞因子水平下降。使用测试浓度(50mM、100mM、150mM)的HC-067047观察到对气道防御反射和气道炎症的影响。HC-067047对气道防御反射和炎症的影响强调了TRPV4通道在哮喘中的作用,并揭示了开发哮喘治疗创新药物的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of TRPV4 channel blocker on airway inflammation and airway defense reflexes in experimentally induced model of allergic asthma

The transient receptor potential (TRP) channels regulate physiological and pathological processes. Changes in their activity and sensitivity may be involved in the pathophysiology of asthma. The present study investigates the effect of an inhaled TRPV4 channel blocker HC-067047 in an experimental guinea pig model of ovalbumin-induced allergic asthma. We monitored the effect of 50 nM, 100 nM, and 150 nM HC-067047 concentrations on airway defense reflexes in vivo and tracheal smooth muscle contractility in vitro. The anti-inflammatory action of HC-067047 was investigated by analysis of chronic inflammation markers from lung homogenates. The results suggest that HC-067047 can suppress airway defense reflexes in vivo and acetylcholine-induced contractility in vitro. Immunological analysis revealed that TRPV4 channel blockade leads to a decrease in the levels of inflammatory cytokines. An effect on airway defence reflexes and airway inflammation was observed using tested concentrations (50 mM, 100 mM, 150 mM) of HC-067047. The effects of HC-067047 on both airway defense reflexes and inflammation underline the role of TRPV4 channels in asthma and uncover therapeutic targets for developing innovative drugs in asthma therapy.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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