基于代谢组学技术研究泽泻抗高脂血症的药效物质基础及其作用机制

Nowadays, hyperlipidemia is seriously affecting human health with a high incidence. Dysregulation of lipid metabolism is the main pathological factor of hyperlipidemia. As a common traditional Chinese medicine, Alisma orientalis exerts a good therapeutic effect on hyperlipidemia, but which fractions possess anti-hyperlipidemic activity and how they intervene these dysregulations of lipid metabolism remain unknown. Our previous studies found that the ethanol extract of Alisma orientalis can treat hyperlipidemia and then total triterpene conponents from the ethanol extract of Alisma orientalis also had a good effect. According to some previous literatures and our studies, we will explore the causes of hyperlipidemia, study the therapeutic effect of ethanol extract and total triterpenes, illuminate their improvement on lipid metabolism-associated protein expression including HMG-CoA, CYP7A1, LDL-R, ACAT and LCAT and ameliorate the lipid biomarkers in hyperlipidemic rats by using the integrative method of pharmacodynamics, pharmacology as well as molecular biology coupled with metabolomic and lipidomic techniques. The study will provide certain reference for biochemical mechanisms of hyperlipidemia, therapeutic effect of ethanol extract and total triterpenes from Alisma orientalis as well as their action mechanism of molecular biology and biomechanical mechanism. Also, this work can supply some basis and targets for discovering new active components of anti-hyperlipidemia from Alisma orientalis and for revealing material basis of effective components of anti-hyperlipidemic effects from Alisma orientalis.

高发病率的高脂血症严重影响着人类健康，脂质代谢紊乱是高脂血症的主要病理因素。泽泻作为一味临床常用中药具有良好的降血脂作用，但是何种活性部位治疗高脂血症及如何干预脂质代谢紊乱仍不清楚。我们曾研究并初步发现泽泻乙醇提取物对高脂血症的防治效果良好，进一步发现泽泻乙醇提取物的总三萜部位对高脂血症也有较好的防治效果。根据文献及我们的研究基础，本课题拟采用药理学、分子生物学、代谢组学和脂质组学方法探讨高脂血症的发病机理及泽泻乙醇提取物和总三萜的治疗效果，阐明泽泻乙醇提取物和总三萜对高脂血症大鼠的脂质代谢相关蛋白HMG-CoA、CYP7A1、LDL-R、ACAT和LCAT表达的影响及脂质生物标示物的改善情况。本项目的完成将为高脂血症生物化学机制的研究、泽泻改善血脂异常的效果及其分子生物学和生物化学作用机制的探究提供参考价值，本研究可为寻找泽泻抗高脂血症的活性成分及揭示其降血脂的药效物质基础提供参考依据。

泽泻（Alismatis Rhizoma）是泽泻科植物泽泻[Alisma orientatle (Sam.) Juzep.]的干燥块茎，临床上常被用于治疗水肿、尿少、高脂血症等疾病。现代研究表明泽泻中含有三萜、倍半萜、生物碱、脂肪酸等化学成分，其中三萜类化合物是泽泻的主要药效成分。《中华人民共和国药典》（2010年版一部）开始，23-乙酰泽泻醇B（泽泻醇B-23-醋酸酯，Alisol B 23-acetate, ABA）被用作泽泻药材和饮片含量测定的唯一指标性成分。药理学研究证明泽泻中的三萜类成分具有利尿、肾保护、肝保护、降血脂等多种生物活性。课题开展泽泻提取物对高脂饮食诱导高脂血症的干预及其生物化学作用机制的相关研究工作。本项目证明泽泻能改善高脂血症大鼠血清中异常的血脂水平；减少高脂血症大鼠主动脉的脂肪积累；改善高脂血症诱导的大鼠异常的肝功能；改善高脂血症大鼠血浆中紊乱的脂质代谢途径；改善高脂血症大鼠异常的尿液代谢产物的代谢途径；泽泻提取物对高脂血症大鼠有较好的改善作用。该项目的完成阐释泽泻治疗高脂血症在脂代谢方面的作用机制，揭示了泽泻治疗高脂血症的药效物质基础；阐明泽泻乙醇提取物和总三萜抗高脂血症的分子生物学和生物化学作用机制。在该基金的支持下共发表SCI论文7篇；获陕西高等学校科学技术奖一等奖；协助培养研究生2名；参与国内学术会议进行交流。