人参与华法林已被广泛应用于心血管疾病的防治，但其临床联用的安全性和有效性仍存在争议，迄今机制尚不清楚。我们前期研究提示长期服用人参皂苷可减弱大鼠体内华法林的抗凝血作用，其机制可能跟调控药物代谢酶CYP2C9和细胞粘附因子ICAM-1等的表达有关。综上本项目提出“人参/人参有效成分可通过调控药物代谢酶及细胞粘附分子等综合改变华法林的药理作用”的假说。拟从分子-细胞-组织和动物水平系统深入研究人参与华法林的相互作用及其机制，主要包括：考察人参/人参有效成分是否改变大鼠体内稳态华法林的抗凝血作用及凝血因子的表达水平；研究人参对华法林整体药效学和药动学等表观参数的影响；阐明药物对代谢关键酶/基因、底物和代谢产物等的作用特点和分子靶标，探讨药物对细胞粘附因子、刺激因子和血小板等的调控机制，最终揭示两种药物潜在相互作用的量效/时效关系及其分子机制。本研究将为心血管疾病防治药物的安全使用提供科学依据。

Ginseng and warfarin have been widely used in the prevention and therapy of cardiovascular disease, but the clinical safety and effectiveness of combined use of two drugs are still controversial, and the underlying mechanism and molecular targets are not clear yet. Our previous studies have showed that ginsenoside can weaken the anticoagulant effect of warfarin, this effect was accompanied by inhibition of drug metabolic enzyme CYP2C9 and cell adhesion molecule ICAM-1 expression. Therefore, we propose the hypothesis: Ginseng/ginseng’s active components can change the pharmacological effects of warfarin by regulating drug metabolism system and cell adhesion signaling pathway. To verify this hypothesis, we will further systematically investigate the interference effect of ginseng and warfarin and reveal its mechanisms on molecular, cell, tissue and animal levels, which includes: To investigate whether the anticoagulation effect of steady state warfarin in rat is changed by ginseng/ginseng’s active components; To analyze the apparent parameters—pharmacodynamics and pharmacokinetics in rat by treatment of ginseng and warfarin; To clarify the characteristics of hepatic drug metabolic enzyme, substrate and metabolite in rat by co-drug treatment; To explore the interference effect of drugs on the key factors of thrombus—platelet, cytokine and cell surface adhesion molecules. Finally, the dosage-effect, time-effect and molecular targets of ginseng and warfarin interaction will be revealed. This study will provide an important scientific basis for the safe application of drugs for the prevention and treatment of cardiovascular disease.