基于Notch通路研究加味六安煎对儿童咳嗽变异性哮喘Th1/Th2功能失衡的干预机制

咳嗽变异性哮喘（CVA）与Th1/Th2功能失衡密切相关，而Notch通路是其上游主要调控通路。我们前期证实加味六安煎治疗该病有效且可调节Th1/Th2平衡，在此基础上提出本假说：“加味六安煎治疗儿童CVA作用机制可能通过调控Notch通路，影响肺组织中T淋巴细胞分化，调节Th1/Th2细胞平衡，介导细胞因子的释放，减轻气道慢性炎症，达到阻逆气道重塑的目的”。本项目拟以CVA豚鼠为研究对象，以Notch通路为切入点，以Notch通路-T淋巴细胞-Th1/Th2细胞-细胞因子-气道结构为主线，采用Western blot、ELISA、电镜等方法，通过观测①咳嗽次数及气道阻力；②Notch通路分子表达（Jagged1、Notch1、NICD、Hes1等）；③细胞因子含量（IL-2、IL-13等）；④气道结构（TGF-β、MMP-9），阐明加味六安煎治疗CVA的上游调控机制，为临床应用提供实验。

Cough variant asthma（CVA） is closely related to the function imbalance of Th1/Th2, and the Notch pathway is the main regulation pathway in the upstream. Our preliminary study found that Jiawei Liuan Decoction can effectively control cough and regulate the balance of Th1/Th2,thus we propose the following hypothesis:“The mechanisms of Jiawei Liuan Decoction in the treatment of children's CVA may regulate the Notch pathway, affect the differentiation of T lymphocytes in the lung tissue, regulate the balance of Th1/Th2 cells, mediate the release of cytokines, reduce airway chronic inflammation, and achieve the purpose of inhibiting airway remodeling”.This research takes the CVA guinea pig as the study object, takes Notch pathway as the breakthrough point, takes Notch pathway-T lymphocyte-Th1/Th2 cell cytokine-airway structure as the main line, and uses Western blot, ELISA , Electron microscope and other methods. By recording①Coughing times and airway resistance②Molecular expression of Notch pathway(Jagged 1,Notch 1,NICD,Hes1 etc)③Levels of Cytokines(IL-2,IL-12 etc)④Airway structure (TGF-beta, MMP-9),we may clarify the upstream regulation mechanisms of Jiawei Liuan Decoction on CVA and provide an experimental evidence for clinical application.