Role of prostaglandin I2 in the bronchoconstriction-triggered cough response in guinea pigs
Role of prostaglandin I2 in the bronchoconstriction-triggered cough response in guinea pigs
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DOI：
10.1080/01902148.2019.1590883
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发表时间：
2019-11-26
影响因子：
1.7
通讯作者：
Nakao, Shinji
中科院分区：
文献类型：
--
作者：
Sakai, Tamami;Hara, Johsuke;Nakao, Shinji
研究目的/目的：吸入氯化乙酰甲胆碱（MCh）可引起支气管收缩和咳嗽。在MCh诱导的支气管收缩后，支气管肺泡灌洗液（BALF）中前列腺素I-2（PGI（2））的代谢产物增加，表明PGI（2）在咳嗽反应中起作用。因此，我们使用实验豚鼠模型来评估PGI（2）在支气管收缩触发的咳嗽反应中的作用。材料与方法：实验一：在暴露于雾化MCh的动物和暴露于雾化盐水的动物中评估BALF中PGF（1）（PGI（2）的稳定代谢产物）的浓度。实验二：吸入MCh后，在3组动物（生理盐水组、低剂量PGI（2）组和高剂量PGI（2）组）中评估支气管收缩和咳嗽。使用增强的间歇（Penh）作为支气管收缩的量度。实验三：在3组动物（给予生理盐水、低剂量PGI（2）受体特异性拮抗剂（IP拮抗剂）和高剂量特异性IP拮抗剂的组）中评估支气管收缩和咳嗽。结果：支气管收缩组BALF中PGF（1）浓度明显高于对照组;在给予高剂量PGI（2）的动物中，MCH诱导的Penh增加显著受到抑制，支气管收缩诱导的咳嗽次数显著减少。在接受高剂量IP拮抗剂给药的动物中，MCH诱导的Penh增加未受影响，咳嗽次数增加。结论：我们的研究结果表明，PGI（2）改善支气管收缩引发的咳嗽。PGI（2）的测量和给药可分别帮助诊断和治疗支气管收缩引发的咳嗽反应。
Purpose/Aim of the study: Methacholine chloride (MCh) inhalation causes bronchoconstriction and cough. Following MCh-induced bronchoconstriction, metabolic products of prostaglandin I-2 (PGI(2)) increase in bronchoalveolar lavage fluid (BALF), suggesting that PGI(2) plays a role in the cough response. Accordingly, we used an experimental guinea pig model to evaluate the role of PGI(2) in the bronchoconstriction-triggered cough response. Materials and Methods: Experiment 1: The concentration of PGF(1), a stable metabolite of PGI(2), in BALF was assessed in animals exposed to nebulized MCh and animals exposed to nebulized saline. Experiment 2: Bronchoconstriction and cough were assessed in 3 groups of animals after MCh inhalation (a saline group, low-dose PGI(2) group, and high-dose PGI(2) group). Enhanced pause (Penh) was used as a measure of bronchoconstriction. Experiment 3: Bronchoconstriction and cough were assessed in 3 groups of animals (groups administered saline, a low dose of a specific antagonist of the PGI(2) receptor (IP antagonist), and a high dose of a specific IP antagonist). Results: The PGF(1) concentration in BALF was significantly higher in the bronchoconstriction group than in the control group. In animals administered high-dose PGI(2), the MCh-induced increase in Penh was significantly suppressed, and the number of coughs induced by bronchoconstriction was significantly decreased. In animals treated with a high dose of an IP antagonist, the MCh-induced increase in Penh was not affected, and the number of coughs increased. Conclusions: Our results suggest that PGI(2) ameliorates a bronchoconstriction-triggered cough. The measurement and administration of PGI(2) may assist in the diagnosis and treatment, respectively, of the cough response triggered by bronchoconstriction.