中文摘要
脂代谢紊乱性疾病严重影响老年人的身心健康,现代医学降脂药副作用多,停药后易反弹。而上一基金发现补肾药淫羊藿苷能改善衰老的脂代谢,且有疗效持久的优势。分子对接提示与核受体PPARβ有关,结合前期基础提出:淫羊藿苷可能通过PPARβ而直接调节衰老脂代谢,并通过多靶点及网络的间接作用重塑脂代谢而产生持久的疗效。.本计划拟应用表面等离子体共振生物传感技术检测淫羊藿苷与PPARβ的亲和力,确定能否结合;以报告基因技术明确其功能性质-激活或抑制;以同位素标记相对和绝对定量研究其生物效应;从药物-靶点论证淫羊藿苷基于PPARβ的降脂机制。同时应用网络药理学技术,从多靶点-网络角度揭示淫羊藿苷疗效持久的机理。本计划充分发挥中医药调节脂代谢的优势,从药物与生物分子的相互识别、信息传递、生物效应及网络药理诠释淫羊藿苷调节衰老脂代谢的科学内涵,有望研究出新作用机制的调脂新药,对于老年心脑血管疾病的防治意义重大。
英文摘要
Lipid metabolism disorder seriously affects the health of the elderly. Lipid-lowering drugs of western medicine have more side effects and more likely to rebound after withdrawal. Our previous studies found that icariin can improve the abnormal lipid metabolism in aging and has long-lasting effect, and indicated the effect is related to the PPARβ. Combined with the previous base, we put forward the hypothesis that icariin regulates lipid metabolism directly by "drug -target" to activate PPARβ, and regulate lipid metabolism indirectly by multi-target network to have a lasting effect..This program will be based on chemical biology and network pharmacology approach. First, surface plasmon resonance (SPR) technology will be used to determine the affinity between icariin and PPARβ receptor. Second, reporter gene technology will be applied to clarify its function. Finally, the isobaric tags for relative and absolute quantitation (iTRAQ) technology will be employed to study its biological effects. This study will illustrate the mechanism of icariin lowering mechanism from "drug - target". Moreover, network pharmacology technology will be applied to research the network mechanisms of icariin regulating lipid metabolism from the "multitarget - network". The program will interpret the scientific connotation of icariin regulating lipid metabolism in aging by the molecules recognize each other between drug and biological target, the transmission of information, biological function and networks. It is expected to work out new mechanisms of lipid-lowering drugs. The program give full play the advantages of Chinese medicine regulating lipid metabolism and has a major significance for preventing and treating cardiovascular and cerebrovascular diseases of the elderly.
