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选择性钠通道蛋白1.7(NaV1.7)阻滞剂PF-05089771对减轻豚鼠变应性鼻炎相关咳嗽的疗效。

Effectiveness of selective NaV1.7 blocker PF-05089771 in reducing cough associated with allergic rhinitis in guinea pigs.

作者信息

Jakusova Janka, Buday Tomas, Mokra Daniela, Barosova Romana, Hanusrichterova Juliana, Adamkov Marian, Mestanova Veronika, Plevkova Jana, Brozmanova Mariana

机构信息

Department of Pathophysiology Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovakia.

Department of Physiology Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovakia.

出版信息

Respir Physiol Neurobiol. 2025 Apr;333:104387. doi: 10.1016/j.resp.2024.104387. Epub 2024 Dec 25.

DOI:10.1016/j.resp.2024.104387
PMID:39730063
Abstract

BACKGROUND

Allergic rhinitis (AR) is a common cause of chronic cough, linked to dysregulated airway C- and Aδ-fibres through inflammatory mediators. Despite the limited efficacy of current antitussive therapies, recent studies show that the Na1.7 inhibitor can block cough in naïve guinea pigs. This study aimed to analyse the effect of the Na1.7 blocker PF-05089771 on cough in guinea pigs with AR.

METHODS

Dunkin Hartley guinea pigs were sensitised and challenged with ovalbumin (OVA). Cough was induced using citric acid aerosol (0.4 M) before nasal challenge (NCH), and then one hour after the 1st, 3rd, and 6th NCH. The OVA-inhibitor group was pre-treated with inhaled Na1.7 blocker (PF-05089771, 100 μM) before tussigen inhalation.

RESULTS

Chronic AR increased cough response to citric acid in both males and females. Pre-treatment with Na1.7 blocker significantly inhibited cough reflex by ≈ 75 % in males and ≈ 80 % in females without affecting respiratory rate.

CONCLUSION

Na1.7 blocker inhalation effectively inhibits cough in guinea pigs with AR.

摘要

背景

变应性鼻炎(AR)是慢性咳嗽的常见病因,通过炎症介质与气道C纤维和Aδ纤维调节异常相关。尽管目前的镇咳疗法疗效有限,但最近的研究表明,Na1.7抑制剂可阻断未致敏豚鼠的咳嗽。本研究旨在分析Na1.7阻滞剂PF-05089771对AR豚鼠咳嗽的影响。

方法

将Dunkin Hartley豚鼠用卵清蛋白(OVA)致敏并激发。在鼻腔激发(NCH)前,以及第1次、第3次和第6次NCH后1小时,使用柠檬酸气雾剂(0.4M)诱发咳嗽。OVA-抑制剂组在吸入诱咳剂前预先吸入Na1.7阻滞剂(PF-05089771,100μM)。

结果

慢性AR增加了雄性和雌性豚鼠对柠檬酸的咳嗽反应。Na1.7阻滞剂预处理可显著抑制咳嗽反射,雄性豚鼠约75%,雌性豚鼠约80%,且不影响呼吸频率。

结论

吸入Na1.7阻滞剂可有效抑制AR豚鼠的咳嗽。

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