"十八反"是中药药性理论的重要组成部分,是古今临床医家用药配伍禁忌的核心内容,几千年来指导和影响着中医临床安全用药.随着人类社会的进步和对医疗健康的需求不断提高,中药安全性问题日益受到社会广泛关注,而"十八反"则是目前中药安全性研究亟待解决的关键科学问题."十八反"中药反与不反的客观界定及其科学本质的阐明,对完善中药配伍禁忌理论,丰富和发展中药配伍理论体系具有重大意义.细胞色素P450酶作为人体重要的I相药物代谢酶系统,对药物代谢和药物之间的相互作用有着重要影响.中药以合并用药为主且其中许多成分或许为P450酶的底物、诱导剂或抑制剂,因此有可能存在基于P450酶的中药相互作用.本课题组将现代药理学中药物相互作用的分子基础P450酶引入中药相互作用的研究,对十八反中各组药物与药物代谢酶的关系进行了较系统的研究,为揭示一类基于药物代谢酶的中药相互作用模式,阐明中药配伍产生相反作用的分子机制和中药十八反配伍禁忌的科学内涵提供了实验依据.%Eighteen incompatible pairs was one of the most important part of the theory of Chinese herbal property theory of TCM, Drug interactions can frequently arise when drugs are coadministered and one drug modulates the metabolic clearance of the second drug through inhibition or induction of a specific CYP enzyme, possibly leading to adverse drug interactions (ADR), including some fatal interactions. Recently, drug-drug interactions based on CYP and the modulated mechanism of CYP by drugs are more concerned. The safety and ADR of Traditional Chinese medicine (TCM) frequently arise with an increasing consumption of TCM, where they are often administrated in combination and the constitutes in herbal preparations maybe substrates, inhibitors or inducers of CYP, so it maybe exist herb-herb interactions based on CYP. CYP, the molecular basis of drug-drug interaction in modern pharmacology was taken into the study of herb-herb interaction. We systemically studied the relationship between eighteen incompatible medicaments and CYP, and the goal of this study was to provide experimental evidences to the mode of herb-herb interaction based on CYP and the mechanism of incompatible medicaments. All these results indicated that compatibility of medicines in a prescription also have herb-herb interaction based on P450. The interaction mode could express as herb may induce or inhibit CYP isozymes, and the modulated CYP isozymes would further have an impact on the metabolism of constitutes in coadmistrated herbs and cause herb-herb interaction.
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