基于NGF/TRPV1信号通路探讨敛肺止咳方治疗间质性肺病相关咳嗽的机理研究

咳嗽和呼吸困难是间质性肺病的主要症状，其中80%以上的间质性肺病患者被顽固性、慢性咳嗽所困扰，而咳嗽也是该类疾病进展的独立预测因子，但目前对间质性肺病相关咳嗽的发生机制缺乏深入探讨。研究表明TRPV1通道的激活可能是间质性肺病相关咳嗽的直接原因，而NGF/TRPV1信号通路则发挥了关键调节作用。本课题组多年来从事间质性肺病和慢性咳嗽的研究，提出肺失敛降、气道挛急、正气亏虚是间质性肺病相关咳嗽的病机假说，经临床证实敛肺止咳方具有较好的止咳作用，推测其机理可能与抑制NGF/TRPV1信号通路激活有关。为了验证这一假说，本课题组拟复制间质性肺病相关咳嗽的豚鼠模型，从咳嗽反应、组织病理学及分子生物学方面，研究间质性肺病相关咳嗽的发病机制，从NGF/TRPV1信号通路的基因蛋白分子表达水平，分析敛肺止咳方对NGF/TRPV1信号通路的影响，阐明间质性肺病相关咳嗽及中药干预的机理及靶点。

Cough and dyspnea are the main symptoms of interstitial lung disease.More than 80% of patients with interstitial lung disease are plagued by intractable and chronic cough.And coughing is an independent predictor of the progression of the disease,however,there is a lack of deeply research on the mechanism of its occurrence.Studies have shown that activation of TRPV1 channels may be a direct cause of cough associated with interstitial lung disease,and the NGF/TRPV1 signaling pathway plays a key role in regulating.Our group has been engaged in the study of interstitial lung disease and chronic cough for many years.We propose that Fei Shi Lian Jiang, Qi Dao Luan Ji,Deficiency of Vital Qi is the pathogenesis of the interstitial lung disease associated cough.It has been proved clinically that the decotion of astringe the lungs and relieve cough treatment has a good curative effect on cough.It is speculated that the mechanism may be related to inhibiting the activation of NGF/TRPV1 signaling pathway.In order to confirm this hypothesis,this study intends to replicate the guinea pig model of interstitial lung disease associated cough,to explore the pathogenesis of interstitial lung disease associated cough from the aspects of cough reaction,tissue pathology and molecular biology.From the expression level of gene protein molecules in NGF/TRPV1 signaling pathway,analyzing the influence of the decotion of astringe the lungs and relieve cough on NGF/TRPV1 signaling pathway,elucidating the mechanism of cough associated with interstitial lung disease and the mechanism and target of Chinese herbal intervention.