四物汤效应成分基于CYP酶的相互作用研究  

In vitro investigation on CYP enzyme based interaction of active components from SIWU decoction

作　　者：谭妍[1] 沈国林[1] 庄笑梅[1] 李桦[1] 高月[2] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《中国药理学通报》2014年第10期1456-1461,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金重点课题(No 81130067);国家"重大新药创制"科技重大专项(No 2012ZX09301003-001)

摘　　要：目的研究四物汤效应成分果糖、阿魏酸、芍药苷和川芎嗪及其配伍对CYP同工酶的抑制及诱导作用,为从代谢角度解释中药方剂的配伍规律提供依据。方法应用人肝微粒体体外孵育模型和探针底物代谢产物的LC-MS/MS定量方法,评价各单药及药对配伍组对CYP酶同工酶CYP1A2、2B6、2C9、2C19、2D6和3A4的抑制作用。应用"三明治"培养的大鼠原代肝细胞模型,评价各单药及其药对配伍组对CYP1A和CYP3A的诱导作用。结果果糖、阿魏酸、芍药苷、川芎嗪及其配伍组(100μmol·L-1),对人肝微粒体CYP1A2、2B6、2C9和2C19的抑制率均<62%,对CYP3A4和CYP2D6的活性无影响。各单药及配伍组对CYP3A1/2无明显的诱导作用;芍药苷及其药对和配伍(50μmol·L-1)对CYP1A2诱导活性的提高>阳性诱导剂的40%。结论四物汤各成分及其药对配伍对6个主要CYP同工酶均无明显的抑制作用,芍药苷单药对CYP1A2有一定诱导作用,与果糖、阿魏酸和川芎嗪配伍时,诱导活性明显增强。Aim To investigate the inhibitory and in-duction effects of the active components of SIWU de-coction on cytochrome P450 enzymes （ CYP ） and as-sess the CYP based drug interaction. Methods Ac-tive components fructose, ferulic acid, paeoniflorin, li-gustrazine and their combinations were incubated sepa-rately with human liver microsomes （ HLM） and probe substrates. Metabolites of the CYP probe substrates were determined by LC-MS/MS to assess the inhibitory activities on human CYP1 A2 , 2 B6 , 2 C9 , 2 C19 , 2 D6 and 3 A4 . Sandwich-cultured rat hepatocytes model was used to evaluate the CYP1 A2 and CYP3 A1/2 induc-tion. Results The inhibitory rates on CYP1A2, 2B6, 2 C9 and 2 C9 by the test groups at 100 μmol · L-1 were all 〈 62%, while the activities of CYP3 A4 and2D6 were not affected. The CYP1A2 activities in the test groups of peoniflorin and its combinations （ 50μmol·L-1 ） were significantly enhanced, with the in-creasing fold more than 40% of positive control group. No significant induction on rat CYP3 A1/2 was ob-served for four principles and their combinations. Con-clusions The active components of SIWU decoction do not show significant inhibitory effects on six CYP isoforms. Peoniflorin could induce the CYP1A2 activity in rat hepatocytes. The induction activity is enhanced by the concomitant use of peoniflorin with ferulic acid and/or ligustrazine.

关 键 词：四物汤 相互作用 细胞色素P450酶 肝微粒体 肝细胞 诱导 

分 类 号：R284.1[医药卫生—中药学] R289.1[医药卫生—中医学]