葛根芩连汤及不同配伍对肝细胞色素P450酶的影响  

Effect of Gegen Qinlian Decoction and different synergies on liver CYP450 isoforms

作　　者：陈烨[1] 袁瑾[1] 王新宏[1] 安叡[1] 肖娟[1] 张宜凡[1] 

机构地区：[1]上海中医药大学,上海201203

出　　处：《中成药》2013年第8期1593-1598,共6页Chinese Traditional Patent Medicine

基　　金：2012年度上海市自然科学基金面上项目(12ZR1431500);2011年度上海市教育委员会科研创新面上项目(11YZ69);高等学校博士点专项科研基金(20093107110011)

摘　　要：目的采用Cocktail探针药物法研究葛根芩连汤(葛根、黄芩、黄连和炙甘草)及其不同配伍对大鼠肝细胞色素P450酶系活性的影响。方法大鼠连续7 d分别灌服葛根组、芩连组、甘草组,尾静脉注射Cocktail探针药物咖啡因、甲苯磺丁脲、右美沙芬、氯唑沙宗、咪达唑仑。建立LC-MS/MS法同时测定大鼠血浆中5种探针药物的浓度,DAS2.0软件计算其药动学参数。结果与空白组比较,全方能诱导大鼠CYP2C6、CYP2D4的活性,抑制CYP2E1的活性,对CYP1A2、CYP3A1/2无影响。葛根组能诱导CYP2C6、CYP3A1/2活性,抑制大鼠CYP2D4及CYP2E1活性。芩连组能诱导CYP2C6的活性,抑制CYP1A2、CYP2D4、CYP2E1的活性。甘草组能诱导CYP1A2、CYP2C6和CYP2D4的活性,抑制CYP3A1/2的活性。结论葛根芩连汤及不同配伍对大鼠CYP450酶的活性影响不同,其中葛根起到主要的作用。AIM To use the cocktail probe drugs to study the effect of Gegen Qinlian Decoction（Puerariae lobatae Radix,Scutellariae Radix,Coptidis Rhizoma,Glycyrrhizae Radix et Rhizoma praeparata cum melle） and its synergies on cytochrome P450（CYP450） isoforms in rats.METHODS The rats respectively received Gegen Qinlian Decoction,Gegen synergy（Puerariae lobatae Radix）,Qinlian synergy（Scutellariae Radix and Coptidis Rhizoma） and Gancao synergy（Glycyrrhizae Radix et Rhizoma praeparata cum melle） for 7 days and were simultaneously injected the cocktail probe drugs including caffeine,tolbutamide,dextromethorphan,chlorzoxazone and midazolam.The plasma levels of the five probe drugs were determined by LC-MS/MS and the main pharmacokinetic parameters were calculated by DAS2.0.RESULTS Compared with the control group,Gegen Qinlian Decoction group had no difference in activity of CYP1A2,CYP3A1/2.It obviously increased the activity of CYP2C6,CYP2D4 and obviously decreased the activity of CYP2E1.The Gegen synergy was significantly increased the activity of CYP2C6,CYP3A1/2 and obviously decreased the activity of CYP2D4,CYP2E1.Qinlian synergy increased the activity of CYP2C6 and significantly decreased the activity of CYP1A2,CYP2D4,CYP2E1.Gancao synergy obviously increased the activity of CYP1A2,CYP2C6,CYP2D4 and could inhibit the activity of CYP3A1/2.CONCLUSION The experiment of Gegen Qinlian Decoction with different compatibility shows different effects on the enzymalic activity of CYP450 and Puerariae lobatae Radix may play a main role in affecting rat＇s liver CYP450 isoforms.

关 键 词：COCKTAIL 葛根芩连汤 CYP450 

分 类 号：R285.5[医药卫生—中药学]