基于“脾病，脉道不利”探讨脾虚痰浊小猪dyHDL对冠脉内皮S1PR1/PI3K/Akt的分子调控机制

In the lipid metabolic abnormalities caused in the pathogenesis of atherosclerosis, HDL is a hotspot for research. In the past people payed attention to the change of HDL “quantity”, now pay more attention to the changes of it’s “quality”. HDL in the oxidation of inflammatory stimuli, the changes in the composition, to carry the S1P reduction as the main feature, the loss of the original anti-AS effect, become with the promotion of inflammation, oxidation, affect the endothelial function loss of the functional HDL. The Spleen transports and transforms the essence of water and food throughout the body, as does lipid transportation rely on the Spleen. Dysfunction of the spleen to transport; such as an insufficient ability to transport excess lipids, leads to an endogenous phlegm turbidity of which progressively leads to an obstruction in blood flow, further defines “leading to unsmooth vessels”. This topic will be guided by the theory of “Spleen disease, leading unsmooth vessels” in Huangdi Neijing, Mini-pig Models of Phlegm Turbidity due to Spleen Deficiency was established by the methods of high fat and single cage feeding. And through the Chinese medicine herb intervention, which invigorates the Spleen to eliminate phlegm, to observe the changes of serum HDL quality and quantity in mini-pigs, will discuss the changes of dyHDL components, and its effects on coronary endothelial function. From dyHDL to S1PR1/PI3K/Akt the adjustment and the control of signaling pathway, elucidate the pathogenesis of dyHDL influence endothelial function to the AS, and clarify the curative effect mechanism of Spleen and eliminating phlegm method, reveals the scientific connotation of “Spleen disease, leading unsmooth vessels”, to provide experimental evidence for clinical treatment of coronary heart disease from Spleen coronary heart disease.

在脂质代谢异常引发的动脉粥样硬化发病机制中，高密度脂蛋白是研究的热点。以往人们关注HDL“量”的改变，现今更重视其“质”的变化。HDL在氧化炎症刺激下，组分发生改变，以携带的S1P减少为主要特征，失去原有抗AS的作用，变成具有促炎、促氧化、影响内皮功能的失功能性HDL。脾主运化水谷精微，脂质亦需脾运化布散周身。脾失健运，不能将多余脂质运化，即内生之痰浊，阻碍血脉运行，即“脉道不利”。本课题将以《内经》“脾病，脉道不利”理论为指导，通过高脂单笼饲养建立脾虚痰浊证小猪模型，并通过健脾祛痰中药干预，观察小猪血清HDL质和量的改变，探讨dyHDL组分的变化、及其对冠脉内皮功能的影响，从dyHDL对内皮S1PR1/PI3K/Akt通路的调控，阐明dyHDL影响内皮功能致AS的发病机制，并阐明健脾祛痰法的疗效机制，揭示“脾病，脉道不利”的科学内涵，丰富脾脏象理论，为临床“从脾论治”冠心病提供实验依据。

在脂质代谢异常引发的动脉粥样硬化发病机制中，高密度脂蛋白是研究的热点。以往人们关注HDL“量”的改变，现今更重视其“质”的变化。HDL在氧化炎症刺激下，组分发生改变，以携带的S1P减少为主要特征，失去原有抗AS的作用，变成具有促炎、促氧化、影响内皮功能的失功能性HDL。脾主运化水谷精微，脂质亦需脾运化布散周身。脾失健运，不能将多余脂质运化，即内生之痰浊，阻碍血脉运行，即“脉道不利”。本课题将以《内经》“脾病，脉道不利”理论为指导，通过高脂单笼饲养建立脾虚痰浊证小猪模型，并通过健脾祛痰中药干预，观察小猪血清HDL质和量的改变，探讨dyHDL组分的变化、及其对冠脉内皮功能的影响，从dyHDL对内皮S1PR1/PI3K/Akt通路的调控，阐明dyHDL影响内皮功能致AS的发病机制，并阐明健脾祛痰法的疗效机制，揭示“脾病，脉道不利”的科学内涵，丰富脾脏象理论，为临床“从脾论治”冠心病提供实验依据。