基于“肺主治节”理论探讨生脉散防治心血管疾病的作用机制研究

The concept of holism, also known as the concept of organic wholeness, refers to the way that Traditional Chinese Medicine (TCM) understands the human body as an unity related with each other. There is a famous statement on the relationship between lung and heart, namely "lung governing management and regulation", it is the most important part of the theory of viscera in TCM. The theory focus on the relationship between lung and heart, or Qi and blood, for lung governs Qi and heart governs blood. According to the theory of Qi and blood of TCM, Qi being commander of blood and Qi promoting blood circulation. Once the function of lung is abnormal, it will inevitably influence the function of heart, such as leading to blood stasis, etc. Shengmai san (SMS) is a famous traditional chinese formula which is composed of Radix Ginseng (Red Ginseng), Radix Ophiopogonis and Fructus Schisandrae. It is widely used in clinical application, especially in all kinds of cardiovascular diseases, such as coronary heart disease, heart failure, arryhthmia, myocarditis, cardiomyopathy, etc. SMS has the characteristics of combining prevention with control and the effects of modulating the function of both lung and heart. Our study inclined to explore the mechanism of action how SMS exerts effects on the cardiovascular diseases through recovering "lung governing management and regulation". In our study, chronic intermittent hypoxia animal model model was selected to simulate the pathological model of "lung not governing management and regulation", the clinical diagnosic index, which reflect the physical and pathological function of lung and heart were both selected to evaluate the dynamic changes of the model, the influence of SMS on the model will be also observed. The cell model which can simulate the damage mechnism of endothelial function of chronic intermittent hypoxia animal model was also studied. Firstly, Our study aimed to testify the accordance of protective effect on endovascular function and preventive effect on pathologic changes of lung and heart induced by chronic intermittent hypoxia. The characteristics of combining prevention with control effect on cardiovascular diseases of SMS will be accurately explained; Secondly, the key pathological link and action point will also be detected, which would not only provide some reference for reasonable and normative application of SMS in clinics, but also accumulate new data for enriching scientific conotation of "lung governing management and regulation";lastly,the pathophysiological mechanism of the classical theory of TCM will be elucidated, and the clinical guiding value would be consequently enhanced.

以整体观为特征的中医学认为心肺密切相关，"肺主治节"体现了肺对血管舒缩以及血液供应的调节功能，是肺主一身之气和心主一身之血功能密切相关的具体体现。本研究借鉴现代医学生理病理诊断指标，拟通过体现"肺主治节"功能失调的慢性间歇性缺氧动物模型和内皮细胞缺氧损伤模型为实验平台，宏观与微观、功能与形态相结合，考察模型动态变化过程中反映肺、血管内皮和心功能形态的指标变化以及生脉散不同时程干预的影响，探讨慢性间歇性缺氧诱导"肺病及心"的病理演变规律及生脉散的作用环节，揭示生脉散促进肺主治节功能重建与血管内皮保护作用的一致性及其防治心血管疾病的优势特色。本课题的顺利实施，将更加准确地阐释生脉散在防治心血管疾病中"防治结合"、"预防为主"的优势特色，为经典复方生脉散及其制剂的合理使用以及临床推广应用积累可靠的实验依据；也将进一步丰富和发展中医"肺主治节"理论的科学内涵；提升中医生理病理学理论的临床指导价值。

生脉散及其制剂在临床上主要作为心绞痛、心肌梗死等疾病稳定期的预防用药以及急性发病后期的巩固、善后用药，通常不作为首选急救药物。本课题从生脉散及其制剂的临床应用现状出发，以体现肺心功能密切相关的经典中医理论“肺主治节”为指导，追溯古方生脉散的源流以及主治疾病谱的历史演变，挖掘出体现其防治结合优势特色的肺心疾病并作为研究切入点，借鉴现代医学与药理学技术方法，实验研究与临床研究相结合，宏观指征与微观指征相借鉴，探讨生脉散防治心血管疾病的可能作用途径及关键作用环节，为生脉散及其制剂的临床推广运用提供合理解释。.首先，以慢性间歇性缺氧（CIH）小鼠模型为实验平台，通过动态检测造模过程中与肺、心功能相关的生理、病理指标的变化，确证CIH小鼠模型肺心同病、先肺后心以及由肺及心的病理变化规律，证实该病理模型模拟“肺主治节”功能失调的可行性。其次，以体现肺、心功能的生理及病理指标为观测对象，考察生脉散不同时程干预对CIH小鼠模型各项指标的影响，评价生脉散促进CIH小鼠“肺主治节”功能重建的作用，确定其防治肺病及心的有效作用环节及可能的作用途径；再次，通过指标间的关联性分析，从中挖掘和遴选出生脉散防治心血管疾病的早期生物标志物。最后，借鉴实验研究结果所确定的生脉散优势病种，制定临床病例观察量表，选择符合条件的临床病例，以实验研究所遴选出的生物标志物为观测指标，考察生脉散干预前后的变化，初步评价其成为心血管疾病早期生脉散干预生物标志物的可靠性。.综上所述，本课题是在中医药理论的指导下，采用现代医学与药理学技术方法相结合、临床研究与实验研究相映证的研究模式，探讨了生脉散在心血管疾病早期发挥防治作用的关键病理环节与作用途径，初步遴选出了心血管疾病早期的生脉散生物学诊断指标。本课题的实施，更加准确地阐释了生脉散在防治心血管疾病中的优势特色，为生脉散及其制剂的合理使用以及临床推广应用积累了可靠的实验依据；也进一步丰富和发展了肺主治节理论的科学内涵。共发表论文5篇，其SCI论文2篇，国内国际会议交流2次，培养硕士研究生2名，博士研究生1名。.