参麦注射液对大鼠肝脏CYP450酶的影响  

Effects of Shenmai injection on the activity of hepatic microsomal CYP450 iszymes in rats

作　　者：张红曦 王宇光[2] 马增春[2] 梁乾德[2] 肖成荣[2] 谭洪玲[2] 汤响林[2] 李桦[3] 沈国林[3] 董志[1] 张伯礼[2] 高月[2] 

机构地区：[1]重庆医科大学,重庆400016 [2]军事医学科学院放射与辐射医学研究所,北京100850 [3]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国新药杂志》2013年第21期2529-2533,2546,共6页Chinese Journal of New Drugs

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

摘　　要：目的:考察参麦注射液及各单药注射液对大鼠肝脏CYP450酶活性及mRNA表达的影响。方法:采用超速离心法制备大鼠的肝微粒体,与探针药物共孵育,应用LC/MS法测定各同工酶特异性底物非那西丁,甲苯磺丁脲,安非他酮,咪达唑仑在大鼠肝微粒体的代谢产物的生成量,间接反映各同工酶的活性。应用RT-PCR方法计算CYP1A2,CYP2B,CYP2C和CYP3A条带灰度与CYC条带灰度的比值,间接反映各处理组亚酶mRNA表达水平的改变。结果:参麦注射液可增加CYP2B6,2C9酶活性,与空白组比较具有显著性差异(P<0.05),对CYP1A2,3A酶活性无明显影响;红参注射液对CYP1A2,2B6和2C9酶活性具有明显诱导作用(P<0.05),对CYP3A酶活性有抑制趋势,无统计学差异;麦冬注射液显著诱导CYP2C9酶活性(P<0.05)。参麦注射液能诱导CYP1A2,2B,2C mRNA表达,红参注射液和麦冬注射液能诱导CYP2C mRNA的表达;红参注射液有抑制CYP3A mRNA表达的趋势,但无统计学差异。结论:参麦注射液及其各单药对CYP450同工酶不同程度的诱导或抑制作用,提示当药物联合应用时应关注可能产生的药物间相互作用。Objective： To investigate the influence of Shenmai injection （SMI） on the activity and mRNA expression of cytochrome P450 （CYP450） system in rat liver microsomes. Methods： Rat liver microsomes were prepared after a fourteen-day continuous administration of SMI. An HPLC-MS method was applied to determine the metabolites formation of six CYP450 probe substrates （phenacetin for CYP1A2, tolbutamide for CYP2C9, bupropion for CYP2B6 and midazolam for CYP3A） in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. A RT-PCR method was applied to determine the mRNA expression levels of CYP450. Results ： SMI significantly induced the activity of CYP2B6 and CYP2C9 （P 〈 0.05） , but did not affect those of CYP1A2 and CYP3A. HSI significantly induced the activity of CYP1A2, CYP2B6 andCYP2C9 （P 〈0.05）, and had an inhibition trend on the activity of CYP3A （not statistically different from control）. MDI induced the activity of CYP2C9 （P 〈 0.05）. At the mRNA level, SMI induced the expression of CYP1A2, CYP2B and CYP2C, while HSI and MDI induced the expression of CYP2C. HSI had an inhibition trend on the expression of CYP3A, but did not statistically differ from control. Conclusion： The possibility of interaction between SMI and coadministrative drugs will be considered base on the levels and subtypes of CYP450 involved in the drug metabolism.

关 键 词：参麦注射液 细胞色素P450酶 COCKTAIL 逆转录聚合酶链式反应 

分 类 号：R969.1[医药卫生—药理学]