基于效应成分原位表征融合小分子探针技术的地菍鞣花单宁“收敛止血”药效物质基础及作用机制研究

地菍为畲族和瑶族的常用止血药，临床用于治疗消化道出血、崩漏等症，其富含鞣花单宁（ETs）类成分，ETs是收敛止血类中药的特征成分，前期研究证明ETs为地菍止血的有效组分，但因其化学结构复杂，相关研究薄弱，其与“收敛止血”传统功效相关的作用机制有待揭示。本研究基于地菍的临床药用，以胃出血和子宫出血模型为载体，以地菍ETs及其体内代谢物为研究对象，聚焦于血内移行和靶组织分布的ETs效应成分，利用质谱成像技术对作用于血管、胃和子宫内膜的ETs效应成分进行原位表征分析，阐明其在多途径发挥止血药效的物质基础，揭示地菍ETs止血过程中“原型成分-代谢成分-效应成分”的变化规律；利用Tissue/blood-TPP小分子探针方法筛选ETs效应成分在血液和靶组织的作用靶点，进而阐明地菍ETs发挥“收敛止血”功效的科学内涵。为含ETs类收敛止血中药的作用机制研究提供科学依据，为中药作用靶点研究提供创新方法。

Diren is a commonly used hemostatic drug for She and Yao people. It is clinically used to treat gastrointestinal bleeding and uterine bleeding. It is rich in ellagitannins (ETs). ETs are characteristic components of astringent hemostatic traditional medicines. Previous studies have proved that ETs are effective components of hemostatic action, but due to the complex chemical structure and lack of related research, the mechanism of action related to the traditional efficacy of "convergent hemostatic" remains ambiguous. This study is based on the clinical usage of Diren, using gastric hemorrhage and uterine bleeding models as carriers, and Diren ETs and its metabolites as research objects, focusing on the ETs effect components in blood and target tissues, using mass spectrometry imaging technique to characterize the in-situ effective components on blood vessels, gastric endometrium and endometrium, to clarify the material basis of the hemostatic effect in multiple pathways, and to reveal the change of ETs from prototype to metabolites, ant to- effective type. In addition, the Tissue / blood-TPP small molecule probe method would be applied to screen the protein targets of ETs effective components in blood and target tissues, which would help to clarify the action mechanism of Diren ETs in stop bleeding. This project will provide scientific reference for the research of ETs contained hemostatic Chinese medicines, and provide innovative methods for the study of drug-target of traditional Chinese medicines.