中文摘要
中药物质基础和体内过程的复杂性,使中药药理和毒性效应及其两者的关系转换研究成为中医药研究的关键科学问题,也是制约中医药学科发展的瓶颈。课题组前期在国家自然科学基金“基于药物代谢酶的中药配伍禁忌研究”等课题资助下,证实孕烷X受体(PXR)能介导药物代谢酶参与中药毒性成分的体内过程,起到减毒增效作用,但产生这种毒-效关系的内在机制值得探寻。基于此,本课题以参附方为研究对象,综合采用常规毒理学和系统生物学方法,从核受体-药物代谢酶(PXR-CYP3A)角度,将参附方的毒-效关系分别与药物煎煮方式、药物剂量和给药时间进行量-毒-时-效整合分析,通过探讨该方物质基础、体内过程、生物效应和毒性机制的变化,阐明参附方配伍禁忌的科学内涵,揭示PXR-CYP3A在参附方毒-效关系转换中的作用和地位,为中药毒-效整合分析研究提供新靶点。该工作将为中药复方毒-效关系转换研究提供示范,为安全合理用药提供科学依据。
英文摘要
Pharmacology and toxicity of traditional Chinese medicine (TCM) and the transformation of both is the key scientific issue due to the complexity of material foundation and digestion of TCM in body. It is also a restricting bottleneck of the development of TCM. With help of the National Science Foundation, in the early research of "Study of incompatibility of traditional Chinese medicine based on drug metabolizing enzymes”, we proved that pregnane X receptor mediate drug metabolizing enzyme which involved in the TCM toxic components digestion in body, plays a role in decreasing toxicity and increasing effect. But the internal mechanism of poison-effect transformation is worth exploring. Hence, we performed a study on Ginseng and Aconite integrated in conventional toxicology and system biology according to nuclear receptor-drug-metabolizing enzymes (PXR-CYP3A), analyzed the dosage, poison, Metabolism time and effectiveness based on the decocting method of drug, drug dosage, and administration time.By exploring the material foundation, in vivo metabolism, biological effects and the change of toxicity mechanism, we clarified the incompatibility of Ginseng and Aconite, revealed the role of PXR-CYP3A in poison-effect transformation of Ginseng and Aconite.This study provides a new target on integrated analysis of TCM poison-effect. It could be an example of the study of TCM poison-effect transformation and provides scientific basis for safe and rational clinical use of TCM.
