基于“肺朝百脉、主治节”理论的Rho/Rho激酶信号通路对COPD肺血管重构的机制研究

Lung Connecting all Vessels and Governing Management and Regulation is important content of visceral manifestations theory of lung, at present study at home and abroad is relatively less,limiting the theory in clinical applications. Clarify the connotation and extension of the theory to guide prevention and treatment lung diseases in TCM is important.Our preliminary studies of pulmonary hypertension in COPD as the starting point,recognizing that the lung Qi deficiency is the initiating factor of COPD,Qi deficiency,phlegm and blood stasis as the key pathological link, to gverning Management and Regulation reconstruction On COPD has a clear effect. Accordingly, we believe that lung to rule section is important to the pathogenesis of COPD,causes pulmonary vascular remodeling and pulmonary hypertension,Pathological mechanism may be closely related to lung qi deficiency, phlegm, and activation of Rho/Rho kinase signaling pathway,In this study visceral manifestations as theory, choose COPD rat model of lung qi deficiency ,phlegm and blood stasis given prescriptions, Regulation of Rho/Rho kinase signaling pathway, clear"Lung Connecting all Vessels and Governing Management and Regulation" theory and the guiding role of prevention and treatment On COPD, to clarify COPD "Lung Connecting all Vessels and Governing Management and Regulation" dysfunction and pulmonary vascular remodeling, revealed TCM interventions for COPD in pulmonary vascular remodeling pathways and the role of target onset,enrich the scientific content of the theory of Tibetan in TCM.

肺朝百脉主治节理论是肺系藏象学的重要内容，目前国内外研究相对较少，限制了该理论在临床中的应用。阐明该理论的内涵与外延，对指导中医药防治肺系疾病具有重要意义。前期研究我们以COPD肺动脉高压为切入点，认识到肺气虚为COPD发病始动因素，"气虚痰凝血瘀"为关键的病理环节，对COPD进行"治节重建"疗效明确。据此我们认为肺朝百脉不利肺失治节为COPD重要发病机理，是肺血管重构、肺动脉高压产生的原因所在，病理机制可能与肺气亏虚、痰瘀阻于肺络激活Rho/Rho激酶信号通路关系密切。本研究拟以中医藏象理论为指导，选择COPD痰瘀阻肺证模型大鼠，给予益气化痰祛瘀方药，调控Rho/Rho激酶信号通路，干预肺血管重构，明确"肺朝百脉主治节"理论内涵及对COPD防治的指导作用，阐明COPD"肺朝百脉主治节"功能失司与肺血管重构相互关系，揭示中医药干预COPD肺血管重构的起效途径和作用靶点，丰富中医藏象理论。

本项目已完成任务书相关研究内容，基本达到预期研究目标。培养硕士研究生1名，已发表核心论文9篇，已录用待发表论文2篇。获得“第四次中华中医药科技成果论坛”优秀论文1篇。. 研究初步明确“肺朝百脉、主治节”理论内涵：肺主治节主要体现肺对呼吸、血液循环、水液代谢、脉管运动等的调节作用。肺朝百脉实质上是肺有调节脉道、运行气血等作用。肺主治节与肺朝百脉功能的正常发挥，是以肺的脏腑之气----肺气为物质基础的，倘若肺气亏虚至一定程度，则肺之“朝百脉、主治节”功能失司，肺疾变生。肺气亏虚、肺失治节、肺朝百脉不利可使Rho/Rho激酶信号通路活化，“肺朝百脉、主治节”功能失司引起Rho/Rho激酶信号通路活化是慢性阻塞性肺疾病肺血管重构发生的主要机理。“益气化痰祛瘀”法可以复使肺之“朝百脉、主治节”功能，芪白平肺胶囊以“益气化痰祛瘀”组方，可以明显改善慢性阻塞性肺疾病模型大鼠的肺功能、降低HIF-1α、PDGF的表达水平，降低Rock-1、Rock-2以及P-MYPT-1的蛋白表达水平。芪白平肺胶囊可以明显降低Rho激酶的表达，减轻慢性阻塞性肺疾病肺血管重构，其干预慢性阻塞性肺疾病肺血管重构的靶点为Rho/Rho激酶信号通路。