基于代谢组学的杏香兔耳风抗宫颈炎药效物质基础及作用机制研究

江西特色优势药材杏香兔耳风用于宫颈炎疗效确切，但物质基础及作用机制不明确是其深入开发利用的瓶颈。在国家自然科学基金资助下，我们已证实杏香兔耳风总酚酸为抗宫颈炎有效部位，且具有抑制解脲支原体和耐药突变菌株作用，通过PK/PD 蒙特卡洛模拟，发现总酚酸抗菌效果优于各二咖啡酰奎宁酸单体，据此推测其可能为多成分和多靶点的起效机制。故本课题拟建立解脲支原体感染小鼠宫颈炎模型，运用UHPLC-MS/MS代谢组学技术，结合MarkerView、MetabolitePilot、PeakView等生物信息学分析方法，建立给药前后的生物样品（如血液、尿液、组织器官等）“代谢物指纹图谱”，探索外源性代谢产物与内源性生物标记物之间的关联，确定代谢途径和代谢通路，并通过活性验证及不同作用途径的比较分析，阐明杏香兔耳风活性物质基础及作用机制。该研究将为杏香兔耳风的二次开发奠定基础，并拓宽抗宫颈炎新药的研发思路。

Ainsliaea fragrans Champ blongs to the dominant herb in JiangXi province which has definite curative effect for anti-cervicitis. But the material basis and action mechanism of this herb were not distinct which have been the bottleneck in its further development. With the support by the National Natural Science Foundation, it had been confirmed that the total phenolic acids were the active ingredients for anti-ureaplasma urealycum and anti-cervicitis in Ainsliaea fragrans Champ. Meanwhile, the experiment result exhibited that it had the inhibitory effect of drug-resistant mutant strain and the antibacterial effect of the total phenolic acid was remarkable comparing with the monomers of dicaffeoylquinic acids which proved by the Pharmacokinetic-Pharmacodynamic models with Monte Carlo simulation. Hence, it was supposed that the curative effect resulted from the coaction of multiple ingredients and the drug targets were also pluralistic. In order to clarify the TCM (Ainsliaea fragrans Champ) metabolic pathways and the action mechanism of multiple ingredients and drug targets, the UHPLC-MS/MS metabonomics technology combined with MarkerView, MetabolitePilot, PeakView and other bioinformatics analysis method would be applied in the experiment research. It can also establish the "Metabolic fingerprinting" of biological samples (such as blood, urine, tissues and organs, etc.) from the animal models with cervicitis before and after the administration. Meanwhile, the relationships between the exogenous metabolites and endogenous biomarkers will be explored. These research efforts will provide the foundation for the secondary development of Ainsliaea fragrans Champ and expand mentality in the new drug research for anti-cervicitis.