慢性咳嗽治疗药物的研究进展缓慢，缺乏理想的慢性咳嗽动物模型是重要原因之一。目前国内外通用的生理性咳嗽模型，因缺乏气道炎症、咳嗽高敏感性与自发性咳嗽，与临床慢性咳嗽相差甚远。本课题组已建立了隧道机动车尾气暴露诱发的慢性咳嗽高敏豚鼠模型，但此模型不易标准化。本研究拟采用机动车尾气室内暴露的方法，首次建立标准化的慢性咳嗽高敏豚鼠模型。通过调节尾气成分、浓度及暴露时间等确定最佳造模条件，使此模型具有与慢性咳嗽患者临床特征相一致的咳嗽高敏感性、自发性咳嗽与非特异性慢性气道炎症，并伴有咳嗽相关的神经肽（SP等）、TRPV1、TRPA1表达和功能增强。同时建立一种新的豚鼠自发性咳嗽评价方法，并探讨TRPV1、TRPA1及非特异性激动剂的组合物能否成为更好的应激性咳嗽激发物。继而，采用此模型对单纯镇咳药物及抗炎药物进行药效学再评价，验证此模型的有效性。本动物模型的建立将有力促进慢性咳嗽治疗新药的研发。

The slow progress of new drugs R&D for chronic cough is related closely with the lack of optional animal models for chronic cough. Because of the absence of airway inflammation, cough reflex hypersensitivity and spontaneous cough, the widely used physiologic cough models are unable to reflect the real condition of chronic cough in clinical practice. By motor vehicle exhaust exposure in tunnel, we have established a guinea pig model of chronic cough with cough hypersensitivity. However, it is difficult to standardize the procedure for this animal model in tunnel condition. This project aims to develop a standard procedure for establishing guinea pig model through indoor motor vehicle exhaust exposure for the first time. The optimal conditions for animal model will be determined through adjusting the exposure time, components, and concentration of exhaust to develop the nonspecific chronic airway inflammation, cough reflex hypersensitivity and spontaneous cough, and increased expression and function of neuropeptides, TRPV1, TRPA1. At the same time, we will establish a new method to assess cough sensitivity in guinea pig model by measuring both spontaneous coughs and stimulated coughs, and determine whether the mixture of TRPV1 agonist capsaicin, TRPA1 agonist AITC, and nonspecific stimulator citric acid, is superior to its single component in evoking cough. Subsequently, the effectiveness of this guinea pigs model of chronic cough will be identified via evaluating the efficacy of available anti-tussives and anti-inflammation drugs. In conclusion, this model will strongly promote the research and development of therapeutic drugs for chronic cough.