Tanaka Motomu, Kawamoto Sadanori, Maruyama Kei
Department of Pharmacology, Faculty of Medicine, Saitama Medical School, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan.
Nihon Yakurigaku Zasshi. 2002 Oct;120(4):237-43. doi: 10.1254/fpj.120.237.
Many studies of cough were performed under the restrained or anesthetized condition, and coughs were evoked by inhalation of capsaicin or citric acid. Inhalation of irritants induced by "diving response" with apnea and coughs, and these responses induced a change of tidal volume. As a result, respiratory responses are dependent on the inhalation volume. Therefore we developed a new coughing model, and coughs were evoked by microinjection of citric acid into the larynx in the unanesthetized unrestrained guinea pig. Microinjection of 7.5% citric acid (2 microliters/30 s, 5 min) induced coughs (27.03 +/- 4.03 coughs/10 min), and citric acid-induced responses were stable independent of the inhalation volume. In the inhalation studies, animals were exposed to citric acid only once because induced-responses were remarkably decreased by repeated administration at an interval of 24 h. However in our coughing model it was possible to repeatedly challenge the animals by microinjection of citric acid at intervals of 24 h. Microinjection of citric acid into the larynx induced coughs in Sprague-Dawley rats, but inhalation of citric acid did not induce cough. These results indicate that this coughing model is highly sensitive and correctly assessed cough responses.
许多咳嗽研究是在约束或麻醉条件下进行的,通过吸入辣椒素或柠檬酸诱发咳嗽。通过“潜水反射”引发呼吸暂停和咳嗽来吸入刺激物,这些反应会引起潮气量的变化。因此,呼吸反应取决于吸入量。因此,我们开发了一种新的咳嗽模型,通过在未麻醉、未约束的豚鼠喉部微量注射柠檬酸来诱发咳嗽。微量注射7.5%柠檬酸(2微升/30秒,共5分钟)可诱发咳嗽(27.03±4.03次咳嗽/10分钟),且柠檬酸诱发的反应稳定,与吸入量无关。在吸入研究中,动物仅暴露于柠檬酸一次,因为间隔24小时重复给药会使诱发反应显著降低。然而,在我们的咳嗽模型中,可以每隔24小时通过微量注射柠檬酸对动物进行重复刺激。向Sprague-Dawley大鼠喉部微量注射柠檬酸会诱发咳嗽,但吸入柠檬酸不会诱发咳嗽。这些结果表明,这种咳嗽模型高度敏感,能够正确评估咳嗽反应。