基于“伏风暗瘀宿痰”哮喘病机新说之搜风愈喘方调控哮喘大鼠气道重塑TGF-β1/VEGF表达的实验研究

Asthma is a chronic allergic airway inflammation characterized by chronic disease, airway remodeling is the pathological basis.Extracellular matrix synthesis and vascular remodeling respectively regulated by transforming growth factor (TGF-β1) and vascular endothelial growth factor (VEGF) induced by Allergic reaction, is an important part of the airway remodeling. Applicant’s asthma pathogenesis new idea " collaterals obstructed by potential Feng stasis and phlegm " corresponds to the western medicine. Based on this, Soufengyuchuan formula has the effective clinical test and the solid early stage research, in which expelling the wind, removing the phlegm and promoting blood circulation to remove blood stasis respectively related with western medicine antiallergy, regulating the extracellular matrix and vascular remodeling. Based on foreign airway remodeling of asthma model experience,this study duplicate the model of chronic asthma, explore the TGF -β1 / VEGF expression and the influence of airway remodeling in asthma; observing this formula and its demolition party function on model rats with airway remodeling and TGF -β1 / VEGF expression regulation; reveal this formula’s intervention on the mechanism of asthma in the level of TGF -β1 / VEGF level and dose effect, clear the target, provide experimental basis for the development of new target asthma drug. By infering the syndrom from a formula to verify the asthma pathogenesis hypothesis of traditional Chinese medicine and the possible modern medicine base.

支气管哮喘是以气道慢性过敏性炎症反应为特征的慢性疾病，气道重塑是其病理基础。过敏反应诱发转化生长因子（TGF-β1）、血管内皮生长因子（VEGF）等分别调控的细胞外基质合成和血管重塑是气道重塑的重要环节。申请人“伏风暗瘀宿痰阻络” 哮喘病机新说与西医哮喘病理相契合，基于此的搜风愈喘方临床验效且前期科研基础扎实，方中祛风、化痰及活血化瘀等法分别与西医的抗过敏、调控细胞外基质和血管重塑相互交通。本研究依据国外哮喘气道重塑模型经验复制慢性哮喘模型，探索TGF-β1/VEGF在哮喘气道重塑中的表达情况及影响；观察本方及其拆方对大鼠气道重塑及TGF-β1/VEGF表达的调控作用；揭示本方在TGF-β1/VEGF层面上干预哮喘机理及其剂量效应，明确其作用靶点，为开发哮喘治疗新靶点药物提供实验依据；通过以方测证法验证哮喘中医病机假说及其可能的现代医学基础。

儿童支气管哮喘是以气道重塑为病理基础的慢性疾病。中医药干预气道重塑研究为中医药防治儿童哮喘的黄金切入点。课题组在前期研究的基础上针对气道重塑进行了深入研究。结果发现：（1）大鼠哮喘模型中血清及肺泡灌洗液中IgE/TGF-β1/VEGF水平与支气管哮喘的严重程度密切相关；（2）搜风愈喘方能下调哮喘大鼠血清、BALF中TGF-β1、VEGF的含量，且抑制其在肺组织中的表达，并能改善肺组织病理及超微结构。这些研究结果提示：搜风愈喘方通过抗过敏、调控细胞外基质和抑制血管重塑机制抑制气道重塑，尤其是下调TGF-β1、VEGF表达抑制细胞外基质和血管重塑作用,验证了哮喘病机新说之“伏风暗瘀宿痰”理论的科学性，完善哮喘中医辨治体系，突破了“内科不治喘”的瓶颈。