基于TGF-β1/Smad信号通路调控的三步序贯法对激素依赖型哮喘气道重塑阻抑作用的研究

气道重塑是激素依赖型哮喘（SDA）的基本特征之一，是导致患者对激素治疗反应性差，形成激素依赖的病理学基础。TGF-β1/Smad信号转导通路被认为是哮喘气道重塑的主要调控途径，调节TGF-β1/Smad信号通路平衡，阻抑TGF-β1胞内信号转导已成为预防或减轻SDA气道重塑的新靶点。既往研究证实，三步序贯法能够有效抑制SDA气道炎症，改善肺功能，减轻患者对激素的依赖性。本项目建立在既往研究工作基础上，以SDA患者和哮喘大鼠气道重塑激素干预模型为研究对象，采用电子支气管镜黏膜活检技术和支气管肺泡灌洗等方法，分别对SDA患者的诱导痰和支气管黏膜活检组织以及模型大鼠的支气管肺泡灌洗液和支气管肺组织进行深入研究，揭示SDA TGF-β1/Smad信号转导通路变化与气道重塑发展水平的相关性，探索三步序贯法对TGF-β1/Smad信号通路的调控作用，阐明三步序贯法阻抑SDA气道重塑的作用机理。

Airway remodeling is one of the basic features of steroid dependent asthma(SDA). It is the leading cause of the poor response to steroid treatment and the pathological basis of steroid dependence.TGF-β1/Smad signal transduction pathway is considered as the main regulatory pathway in airway remodeling in asthma .Modulation of TGF-β1/Smad signaling pathway and inhibition of TGF-β1 intracellular signal transduction have become a new target to prevent or mitigate the airway remodeling in SDA .Previous studies have confirmed that three stage sequential therapy could effectively inhibit the airway inflammation in SDA ,improve the lung function and alleviate the patient steroid dependence. Based on these findings, this project focuses on the induced sputum and bronchial mucosal biopsies of the SDA patients and the bronchoalveolar lavage fluid and bronchial lung tissues of rat models with SDA by means of electronic bronchoscopy and bronchoalveolar lavage,aiming to reveal the relevance between the TGF-β1/Smad signaling pathway and airway remodeling,to explore the regulatory effect of three stage sequential thrapy on TGF-β1/Smad signaling pathway and to clarify the mechanism of the method in inhibiting the airway remodeling in SDA.