中药名方二仙汤调节脂代谢紊乱的物质基础及其作用通路研究

The Er-Xian decoction, as renowned traditional Chinese herbal medicine, is mainly applied for the treatment of menopause. As the lipids metabolic disorder, postmenopausal women tend to have a higher risk in developing obesity. According to the previous literature, Er-Xian decoction has been proved as an effective TCM for regulating the perturbed pathways of lipids. However the active chemical components in this decoction contributed to the regulating lipids metabolism as well as the perturbed pathway of lipids are still in research. Herein, we will apply a new way to screen the active components in Er-Xian decoction and endogenous lipids based on the combination of Mass Spectrum Tree Similarity Filter (MTSF) with Lipids Data Analyzer built in our lab. The point of this project is to study the relationship between the active components and endogenous lipids in ovariectomized rats. In addition, all data will be analyzed related to the changes of estrogen and pharmacodynamics evaluation. This project is looking for the main group of components in Er-Xian decoction which have pharmacodynamics effect as well as pathways of action. All results expected will reveal the main mechanism of chemical components in Er-Xian decoction by the combination of phytochemistry, pharmacodynamics, pharmacokinetics as well as lipidomics.

中药名方二仙汤主治妇女绝经前后诸症。绝经后妇女，体内脂代谢常发生紊乱，患有肥胖病的风险显著提高。有研究报道，二仙汤具有调节绝经后脂代谢紊乱的作用，但尚不清楚其调节脂类代谢变化的物质基础和具体调节的脂代谢通路。本项目通过整合申请人所在课题组前期研发的质谱树状图相似度过滤（mass spectral trees similarity filter，MTSF）技术和Lipid Data Analyzer数据分析平台，研究进入双侧去卵巢大鼠模型体内的二仙汤物质成分和内源性脂类化合物的整体代谢变化。结合雌激素测定结果和药效学评价指标，采用生物统计学方法，找到与药效相关的二仙汤体内物质和内源性脂类化合物，从体内代谢网络角度揭示二仙汤的药效物质基础和作用通路，探索性地将植物化学-药效学-药代动力学，以及脂质组学研究关联起来。

中药名方二仙汤主治妇女绝经前后诸症。绝经后妇女，体内脂代谢常发生紊乱，患有肥胖病的风险显著提高。本项目通过研究进入双侧去卵巢大鼠模型体内的二仙汤物质成分和内源性脂类化合物的整体代谢变化，结合雌激素测定结果和药效学评价指标，采用生物统计学方法，找到与药效相关的二仙汤体内物质和内源性化合物，从体内代谢网络角度揭示二仙汤的药效物质基础和作用通路，探索性地将植物化学-药效学-药代动力学，以及靶向代谢组学研究关联起来。在项目研究过程中，建立了多个具有创新性的分析技术策略，包括中药体内物质识别和鉴定技术，体内激素分析测定平台等。相关文章发表在药物代谢领域顶级杂志Drug Metabolism and Disposition和分析化学领域顶级杂志Analytical Chemistry上，均标识了基金资助，很好的完成了项目任务书。另外在青年基金资助执行期间，项目承担人还以第一作者或者通讯作者发表SCI论文6篇（未标识青年基金资助号）。