基于体内过程的“痛风汤散”抗痛风作用物质基础和机制研究

针对痛风疾病发病率高、治愈率低的特点和一线临床尚缺少高效安全药物的现状，课题组在前期研究中发现传统藏药“痛风汤散”具有显著的抗痛风作用，但其抗痛风效应成分和作用机制迄今尚不清楚。因此，本课题基于传统藏药的挖掘开发目的，以痛风“尿酸升高和炎症”关键病理环节为切入点，整合现代药理学、血清药物化学、生物信息学和代谢组学等技术，并基于体内过程从整体、组织、分子层面研究“痛风汤散”对尿酸生成酶、尿酸转运体、炎症因子的调控作用；继而利用UPLC-MS/MS技术和Peakview、MarkerView以及MetaboAnalyst等分析方法获得内源性生物标志物和“痛风汤散”的外源性代谢产物，并对“内源生物标志物与痛风生物效应”、“外源代谢产物与抗痛风药效”进行关联性分析，明确痛风的主要生物标志物和代谢通路以及“痛风汤散”抗痛风的效应成分与作用机制，为其临床应用提供基础依据。

In view of the high incidence and low cure rate of gout and the lack of effective and safe drugs in the first-line clinical practice, the research team found that the traditional Tibetan medicine "TongFengTangsan" has significant anti-gout effect in the former study, but its anti-gout effective components and mechanism are still unclear. Therefore, based on the key pathological links - "uric acid elevation and inflammation" of gout, this subject integrates modern pharmacology, serum pharmacochemistry, bioinformatics and metabonomics, and studies the effects of "TongFengTangSan" in vivo on the regulation of uric acid-producing enzymes, uric acid transporters and inflammatory factors from the whole, tissue and molecular levels. Then the endogenous biomarkers and exogenous metabolites of "Tongfeng Tangsan" were obtained using UPLC-MS/MS technology and Peakview, MarkerView, MetaboAnalyst and other analytical methods. Then, the correlation between "endogenous biomarkers and biological effects of gout", "exogenous metabolites and anti-gout efficacy" was been constructed for the analysis of the main biomarkers, metabolic pathway, the anti-gout components and mechanism of Tongfeng Tangsan. It will provide the basis for its clinical application.