疏肝清脂法干预PI3K/Akt信号通路在动脉粥样硬化中的分子机制研究

摘要

Disorder Lipid metabolism is an important reason of causing atherosclerosis (AS). PI3K/Akt signal routing is point of convergence which influence many factors of AS to excite intracellular signal. Traditional Chinese medicine believes that failure of the liver to govern free flow of qi is the main reason of AS caused by disorder lipid metabolism. Preliminary studies indicated that soothing the liver and eliminating lipid method is effective measure to intervene occurrence and development of AS. This project via signal transduction networks research strategy to influence the common regulatory point PI3K/Akt signal routing of many factors of occurrence of atherosclerosis as an entry point. Animal models of atherosclerosis and vascular smooth muscle cells (VSMC) is the object of study , using molecular biology, serum pharmacology and other technical, studying soothing the liver and eliminating lipid method of intrinsic link and feedback mechanism about VSMC signal associated protein and its substrates gene and protein expression, exploring soothing the liver and eliminating lipid method intervene PI3K/Akt signal routing to inhibit VSMC proliferation and migration in mechanism of occurrence of AS, further evidencing feasibility of new target ofPI3K/Akt signal transduction regulation as improving lipid metabolism to delay occurrence of AS, for the screening selectivity of Traditional Chinese Medicine intervene PI3K/Akt signal transduction lead to delay occurrence of AS to provide reliable experimental methods and theoretical basis, while providing new ideas and methods to enrich pathogenetic mechanisms and theory of therapeutic method of AS .%脂质代谢异常是引起动脉粥样硬化(AS)的重要原因,PI3K/Akt信号通路是影响AS诸多因素激发胞内信号的汇聚点.中医学认为肝失疏泄是脂质代谢异常引发AS的主要原因,前期研究表明疏肝清脂法可有效干预AS的发生和发展.借助信号转导网络研究策略,以影响AS发生的诸多因素的共同调控点PI3K/Akt信号通路为切入点,以AS动物模型和血管平滑肌细胞(VSMC)为研究对象,运用分子生物学、血清药理学等技术,研究疏肝清脂法对VSMC信号相关蛋白及其底物的基因及蛋白表达的内在联系和反馈机制,探讨疏肝清脂法干预PI3K/Akt信号通路抑制VSMC增殖和迁移在AS中的作用机制,进一步证明PI3K/Akt信号转导调控作为改善脂质代谢延缓AS发生的新靶点的可行性,为筛选具有选择性干预PI3K/Akt信号转导而延缓AS发生的中药提供可靠实验手段和理论依据,同时为丰富AS的发生机制与治法理论提供新的思路与方法.