大黄苷元对大鼠药物代谢酶CYP2A6、CYP3A4活性的影响  

Evaluation of the anthraquinones from Radix et Rhizoma Rhei on activity of liver microsomal cytochrome P2A6 and cytochrome P3A4 in rats

作　　者：冯素香[1] 王蒙蒙[1] 吴兆宇[1] 李先[1] 郝蕊[1] 徐艳华[1] 

机构地区：[1]河南中医学院,河南郑州450046

出　　处：《暨南大学学报（自然科学与医学版）》2014年第6期513-518,共6页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：国家自然科学基金资助项目(81274179)

摘　　要：研究大黄苷元对大鼠体内药物代谢酶CYP2A6、CYP3A4活性的影响,以预测大黄与临床常用药物的相互作用.大鼠分组,分别灌胃不同质量浓度大黄苷元、质量分数0.5%羧甲基纤维素钠(CMC-Na)、苯巴比妥钠(PB)、地塞米松(DEX)、β-奈黄酮(β-NF)和酮康唑(KET),取各给药组给药后24 h的肝微粒体(RLM)与CYP2A6、CYP3A4的探针底物香豆素、睾酮进行体外温孵,通过高效液相色谱法分别测定各底物的代谢产物7-羟基香豆素、6β-羟基睾酮的生成量,考察大黄苷元对CYP2A6、CYP3A4活性的影响.大黄苷元高、中、低剂量给药组代谢产物7-羟基香豆素的生成量高于空白给药组和KET给药组,均有统计学意义(P<0.05)、(P<0.01),大黄苷元高剂量给药组代谢产物6β-羟基睾酮的生成量高于空白给药组和KET给药组,均有统计学意义(P<0.05)、(P<0.01).随着大黄苷元给药剂量的增加,7-羟基香豆素、6β-羟基睾酮的生成量均随之增加.大黄苷元对CYP2A6、CYP3A4均有诱导作用,并且随着大黄苷元剂量的增加,其对CYP2A6、CYP3A4诱导作用均增强.To evaluate the anthraquinones from Radix et Rhizoma Rhei impact on CYP3A4 and CYP2A6 activity in rats and to forecast the drug-drug interaction with it.SD rats were randomly grouped, Giving 0.5% sodium carboxymethyl cellulose(CMC-Na)、phenobarbital phenobarbital sodium(PB)、dex-amethasone(DEX)、beta-naphthoflavone(β-NF)、ketocon-azole (KET)and different dosages of Rhubarb aglycone respectively to them.Blending and incubating each dose group liver microsome of 24 after treat-ment with the probe of CYP2A6、CYP3A4.Meanwhile,the production of the two probe were detected by HPLC.The metabolites of Rhubarb aglycone high,medium and low dosage groups were higher than the blank group and KET group,both had statistical significance(P <0.05)、(P <0.01 ),the metabolites generation of rhubarb aglycone high dosage groups was higher than the blank and KET group,both had statistical significance(P <0.05)、(P <0.01),Along with the increasing dosage of rhubarb aglycone,the production of 7-hydroxycoumarin,6β-hydroy testosterone were increased.Both CYP2A6 and CYP3A4 can be induced by rhubarb aglycone,With the increase dosage of rhubarb,its induced function were en-hanced.

关 键 词：大黄苷元 CYP2A6 CYP3A4 肝微粒体 诱导 

分 类 号：R285.5[医药卫生—中药学]