基于临床用量的参附注射液对大鼠肝脏主要药物代谢酶的影响  

Effect of Shenfu injection on CYP450s of rat liver

作　　者：李晗[1,2] 王宇光[2] 马增春[2] 周思思[2] 梁乾德[2] 肖成荣[2] 谭洪玲[2] 汤响林[2] 李桦[2] 沈国林[2] 张伯礼[1] 高月[2] 

机构地区：[1]天津中医药大学,天津300193 [2]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《药学学报》2013年第5期728-733,共6页Acta Pharmaceutica Sinica

基　　金：国家重点基础研究发展计划资助项目(2012CB518402;2011CB505304)

摘　　要：考察参附注射液对大鼠肝脏药物代谢酶(CYP450)酶活性的影响及在mRNA水平的调控作用。取SD大鼠,给予受试药物后,采用Cocktail体外孵育法结合液质联用技术对大鼠肝中1A2、2B、2C和3A各亚酶的酶活性进行测定,并利用RT-PCR技术对上述亚型的mRNA水平表达进行检测。参附注射液组可以显著诱导CYP2B、2C11酶活性,对1A2和3A酶活性具有抑制作用。在mRNA水平上,参附注射液可以显著诱导2B和2C11的基因表达,对1A2和3A出现抑制作用,与酶活性水平具有一致性。基于临床用量的参附注射液对大鼠肝脏P450的特定亚型在酶活性水平具有调控作用,并且这种作用可能起始于转录环节,可能与参附注射液配伍增效有关,当与其他药物合用时有可能产生药物相互作用。The paper is to report the study of the effect of Shenfu injection on the enzyme activity of liver CYP450 and its mRNA level of rat liver. Microsome of rat liver was prepared after intravenous administration of Shenfu injection for 7 days. The enzyme activity was quantified by Cocktail method. Meanwhile, the mRNA expression of CYP1A2, CYP2B1/2, CYP2Cll and CYP3A1 in the liver was detected by RT-PCR. Shenfu injection obviously induced the enzyme activities of CYP2B and CYP2C. Meantime Shenfu injection decreased the enzyme activities of CYP1A2 and CYP3A. The mRNA levels of CYP2B and CYP2C were also induced in rats treated with Shenfu injection. But it obviously inhibited the mRNA level of CYP1A2 and CYP3A. Since the enzyme activity and mRNA level were obviously changed after administration, the potential effect of drug-drug interaction should be concerned.

关 键 词：参附注射液 细胞色素P450 肝微粒体 

分 类 号：R969[医药卫生—药理学]