项目名称： 基于双位点微透析-代谢组学的沙棘膏预防低氧性肺动脉高压的物质基础及作用机制研究

项目编号： No.81503361

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： 杜蕾蕾

作者单位： 成都中医药大学

项目金额： 18万元

中文摘要： 沙棘膏是藏药治疗肺部疾病的要药，现代研究表明其对低氧性肺动脉高压（HPH）具有较好的预防效果，但相关的药效物质基础和作用机制尚不明确。本项目拟在前期研究基础上，以血、肺双位点微透析-UPLC-Q-TOF/MS代谢组学为核心技术，从“化学指纹谱-内源性代谢物谱-药物代谢成分谱”多维角度阐明沙棘膏防治HPH的药效物质基础和作用机制。首先，建立沙棘膏不同样品的化学指纹图谱；其次，基于低氧通气HPH大鼠模型，研究沙棘膏的干预效果，确定血、肺双位点药物代谢成分及内源性生物标志物，并根据标志物的代谢通路分析，阐明沙棘膏防治HPH的作用机制。最后，结合沙棘膏化学指纹图谱，应用数据挖掘技术逆向追踪，找出药物代谢成分谱中与生物标志物相关联的化合物类群，阐明沙棘膏防治HPH的药效物质基础。本课题的实施不仅能够从整体层面阐释沙棘膏对HPH发生、发展过程的干预和影响，还可以为沙棘膏的深度开发利用提供科学依据。

中文关键词： 沙棘膏；低氧性肺动脉高压；微透析；代谢组学；物质基础

英文摘要： Seabuckthorn paste，an important Tibetan medicine commonly used for pulmonary disease，showed impressive protective effect on hypoxic pulmonary hypertension (HPH) in several recent pharmacological studies. However, the relevant active substances and mechanism is not clear yet. Our project, based on previous experiments, intends to address this issue by constructing “chemical fingerprint chromatograph - endogenous metabolites chromatograph – medicinal metabolites chromatograph” network with two-site (blood and pulmonary interstitial fluid) microdialysis hyphenated UPLC-Q-TOF/MS metabonomics technique. First, a fingerprint chromatograph of seabuckthorn paste samples will be established. Then, protective effect of seabuckthorn paste will be studied with HPH rats induced by hypoxic ventilation. In addition, through identification of medicinal metabolites and endogenous biomarkers in samples from blood and pulmonary interstitial fluid, combined with analysis of metabolic pathway of biomarkers, protective mechanism of seabuckthorn paste will be characterized. Last, compound groups relevant to biomarkers in medicinal metabolites chromatograph are to be found out by reverse tracking with data mining technique in order that active substances against HPH will be identified. The implementation of this protocol will not only characterize protective effect of seabuckthorn paste on HPH pathological progress from a holistic perspective, but also provide scientific evidence supporting comprehensive development and utilization of seabuckthorn paste.

英文关键词： seabuckthorn paste;hypoxic pulmonary hypertension;microdialysis;metabonomics;material basis