三七中原人参二醇型和原人参三醇型皂苷抗动脉粥样硬化作用及其机制研究

项目名称： 三七中原人参二醇型和原人参三醇型皂苷抗动脉粥样硬化作用及其机制研究

项目编号： No.81503288

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 万建波

作者单位： 珠海澳大科技研究院

项目金额： 18万元

中文摘要： 以动脉粥样硬化为基础的心脑血管疾病严重危害人类健康，中药三七总皂苷（PNS）及其制剂抗动脉粥样硬化的效果较为明确，根据分子母核不同，PNS可分为原人参三醇型皂苷（PTS）和原人参二醇型皂苷（PDS）。前期工作观察到：PNS能显著减少高脂饮食诱导的apoE缺陷小鼠动脉粥样硬化的形成；体外实验表明PDS表现比PNS和PTS更强的抗血管炎症活性，提示PDS可能在体内具有更好的抗动脉粥样硬化效果。本项目利用高脂诱导的apoE缺陷小鼠模型及客观的en-face斑块评价手段，在体内研究并比较PTS和PDS对动脉粥样硬化的影响，从NF-κB和MAPK信号通路进行血管炎症作用机制的阐述。并且利用UPLC/Q-TOFMS代谢组学技术，从干预代谢的角度，进一步研究PDS 和PTS 抗动脉粥样硬化作用机制及相关代谢通路的影响。本项目研究成果将为从中药三七中开发新型的抗动脉粥样硬化药物提供科学依据。

中文关键词： 人参皂苷；原人参三醇型皂苷；原人参二醇型皂苷；动脉粥样硬化；血管炎症

英文摘要： Atherosclerosis is the underlying pathology of cardiovascular diseases (CVD), the leading cause of death worldwide. Panax notoginseng and its preparations have been traditionally applied to clinic for the prevention and treatment of CVD. The therapeutical effect attributes to P. notoginseng saponins (PNS), which could be classified into 20(S)-protopanaxatriol (PTS) and 20(S)-protopanaxadiol saponins (PDS) according to their skeleton of their aglycones. Our previous in vivo study has demonstrated that PNS notably decreased the formation of atherosclerotic plague in the apoE-/- mice fed high-fat diet, and the in vitro study showed that PDS exhibit the more potent effect on anti-vascular inflammation, comparing to PTS and PNS. Therefore, a long-term goal of present proposal is to evaluate and compare the anti-atherosclerotic effects of PTS and PDS in apoE-/- mice fed high-fat and high-cholestrol diet using an en-face method for plaque evaluation, and to elucidate the underlying mechanisms involving NF-κB and MAPK pathway-based vascular inflammation. Finally, using UPLC/Q-TOFMS-based metabolomics approaches, the metabolic biomarkers of atherosclerosis will be identified, and which metabolic pathway intervened by PTS and PDS in the prevention of atherosclerosis will be also investigated in order to reveal their underlying mechnisams from metabolic aspect. Our findings of present proposal will provide the scientific evidence for the development of new class potential anti-atherogenic drugs from P. notoginseng.

英文关键词： Ginsenosides;20(S)-protopanaxatriol saponins;20(S)-protopanaxadiol saponins;atherosclerosis;vascular inflammation