基于"肺气虚失治节"理论的慢性阻塞性肺疾病K-ATP通道抑制与肺血管收缩机制的研究

Theory of〝Lung Governing Management and Regulation〞highly generalized physiological functions of the lungs. if there is enough Lung qi,Lung can rule the action of Management and Regulation.nevertheless,if Lung qi Deficiency,Lung missed the action of Management and Regulation.〝Qi deficiency,phlegm and blood stasis〞is important pathogenesis about a variety of pulmonary diseases,such as COPD.Years of research shows that〝Lung missed the action of Management and Regulation〞can reconstruction by Intervention of traditional Chinese Medicine. Our previous study found,prescriptions Treatment for phlegm and blood stasis is the most effective way to achieve reconstruction of 〝Lung Governing Management and Regulation〞, But the mechanism still need to discuss.Modern research confirms, pulmonary vasoconstriction is the major mechanism of COPD complicated with pulmonary hypertension,while hypoxia is the root cause of inhibiting the K-ATP channel leading to pulmonary vasoconstriction. We think that lung qi deficiency,Lung missed the action of Management and Regulation in COPD is the main pathogenesis of inhibiting the K-ATP channel induced pulmonary vasoconstriction.VISCERAI manifestation theory guided this study,we choose COPD rat model of lung qi deficiency,regulate the K-ATP channel,intervent COPD pulmonary vasoconstriction,Reduct the pulmonary artery hypertension, clear the theory connotation and guiding role about〝Lung Governing Management and Regulation〞on COPD control,elucidate the relationship of pulmonary vasoconstriction and K-ATP channel during COPD reconstruction of Lung Governing Management and Regulation, Reveal the channel and targets of traditional Chinese medicine interventing COPD pulmonary vasoconstriction,innovate and enrich the visceral manifestation theory.

肺主治节是对肺生理功能的高度概括，治节功能是通过肺主气而行使的，肺气虚则肺失治节，顺次发生的"气虚痰凝血瘀"是多种肺系疾病如肺胀等的关键病理环节和重要发病机理。多年研究表明，肺失治节可以应用中药干预进行治节重建。既往研究发现益气化痰祛瘀方药是实现治节重建的最有效途径，但其作用机理尚待探讨。现代研究证实，肺血管收缩是肺胀（COPD）并发肺动脉高压的主要机制，而低氧是抑制K-ATP通道导致肺血管收缩根本原因。COPD肺气虚失治节是抑制K-ATP通道致肺血管收缩的主要病机。本研究选择COPD痰瘀阻肺证模型大鼠，通过有效干预，实现治节重建以此调控K-ATP通道，抑制肺血管收缩，降低肺动脉高压，从而进一步明确"肺主治节"理论内涵及对COPD防治的指导作用，阐明COPD治节重建过程中K-ATP通路与肺血管收缩相互关系，揭示中医药干预COPD肺血管收缩的起效途径和作用靶点，创新和丰富中医药理论。

课题组探讨了益气化痰祛瘀方——芪白平肺胶囊对慢性阻塞性肺疾病大鼠KATP通道抑制与肺血管收缩作用和机制。主要研究内容与研究结果如下：.1）通过理论研究，初步明确“肺主治节”理论的关键内涵。“肺主治节”是对肺生理功能的高度概括，治节功能是通过肺主气而行使的，肺气虚则肺失治节，顺次发生的“气虚痰凝血瘀”是多种肺系疾病如肺胀等的关键病理环节和重要发病机理。.2）动物实验建立COPD痰瘀阻肺证模型大鼠，通过芪白平肺胶囊有效干预，确证芪白平肺胶囊能有效改善COPD肺功能、降低平均肺动脉压，降低血清CAM-2及VEGF含量，上调Kir6.1、 SUR2B mRNA及SUR2B蛋白的表达。.3）离体血管实验结果显示，芪白平肺胶囊有明显舒张肺血管作用，且与KATP通道开放有关。.4）细胞实验结果显示，KATP通道的开放受缺氧时间和程度的影响，芪白平肺含药血清能显著上调肺动脉平滑肌细胞Kir6.1和SUR2B蛋白的表达，进一步明确芪白平肺胶囊是一种KATP通道开放剂，参与肺血管舒张作用。课题通过系列研究，明确了“肺主治节”的理论内涵及对COPD防治的指导作用，阐明COPD治节重建过程中KATP通道与肺血管收缩相互关系，为中医药防治COPD提供理论和实验依据。