穿心莲片对华法林药代动力学的影响及机制研究  

Effects of Chuanxinlian tablets on the pharmacokinetics of warfarin and its mechanism

作　　者：俞晓艳 王蓉[1] 宋复兴 陈松 原永芳[1] YU Xiao-yan;WANG Rong;SONG Fu-xing;CHEN Song;YUAN Yong-fang(Department of Pharmacy,Shanghai Ninth People’s Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 201999)

机构地区：[1]上海交通大学医学院附属第九人民医院药剂科

出　　处：《中南药学》2020年第1期68-73,共6页Central South Pharmacy

基　　金：上海交通大学医学院药学科研基金(编号：JDYX2017QN008)

摘　　要：目的研究穿心莲片对华法林药代动力学的影响,以及穿心莲有效成分穿心莲内酯、新穿心莲内酯、脱水穿心莲内酯和脱水穿心莲内酯琥珀酸半酯对Chang Liver细胞CYP3A4和CYP2C9表达的影响,并探索穿心莲片影响华法林代谢的机制。方法采用HPLC-MS/MS检测穿心莲片对华法林药代动力学的影响;RT-PCR法和Western blot法分别检测穿心莲有效成分对Chang Liver细胞中CYP3A4、CYP2C9 mRNA和蛋白表达的影响。结果在SD大鼠体内,穿心莲片可抑制华法林的代谢,穿心莲内酯、脱水穿心莲内酯、脱水穿心莲内酯琥珀酸半酯和新穿心莲内酯可降低CYP3A4、CYP2C9 mRNA和蛋白表达(P<0.05)。结论穿心莲和华法林联合用药的药代动力学研究结果发现,穿心莲片能够抑制华法林在大鼠体内的代谢,这可能与穿心莲成分穿心莲内酯、脱水穿心莲内酯、脱水穿心莲内酯琥珀酸半酯和新穿心莲内酯降低CYP3A4及CYP2C9酶的表达有关。Objective To determine the effect of Chuanxinlian tablets on the pharmacokinetics of warfarin,and effect of the effective ingredients of Chuanxinlian tablets(andrographolide,neoandrographolide,dehydroandrograph and dehydroandrographolide succinate)on the expressions of CYP3A4 and CYP2C9 in Chang Liver cells,and to explore the mechanism of the active ingredients on cell vitality and metabolism.Methods HPLC-MS/MS was performed to determine the effect of Andrographis tablets on the pharmacokinetics of warfarin.RT-PCR and Western blot were used to examine the gene and protein expression levels of CYP3A4 and CYP2C9,respectively.Results Chuanxinlian tablets inhibited the metabolism of warfarin in SD rats.Andrographolide,dehydroandrograph,ehydroandrographolide succinate and neoandrographolide decreased the gene and protein expression levels of CYP3A4 and CYP2C924 hours after the Chang Liver cells were treated(P<0.05).Conclusion Pharmacokinetic study shows that Chuanxinlian tablets can inhibit the metabolism of warfarin in rats.Further research on CYP450 enzymes confirms that the molecular mechanism of warfarin inhibiting the metabolism of warfarin is closely related to reducing CYP3A4 and CYP2C9 enzymes activity.

关 键 词：穿心莲片 华法林 药代动力学 Chang Liver细胞 CYP450 

分 类 号：R969[医药卫生—药理学]