应用大鼠肝微粒体筛选对细胞色素P4502D6有抑制作用的中药  

Screening of Chinese materia medica possessed inhibitory effect on cytochrome P4502D6 in liver microsomes of rats

作　　者：于卫江[1,2] 黄丽军[1] 朱大岭[1,2] 

机构地区：[1]哈尔滨医科大学附属第二医院临床药学药物研究所 [2]哈尔滨医科大学药学院黑龙江省生物医药工程重点实验室,黑龙江哈尔滨150081

出　　处：《中草药》2007年第3期397-401,共5页Chinese Traditional and Herbal Drugs

基　　金：国家"863"课题(2002AA2Z3410);黑龙江省自然科学基金重点资助项目(ZJY03-08);哈尔滨医科大学研究生创新基金资助项目

摘　　要：目的从17种中药(单体、提取物和注射液)中快速筛选出对细胞色素P4502D6(CYP2D6)亚型有抑制作用的中药,建立高通量筛选对CYP2D6有抑制作用中药的技术平台。方法取大鼠空白肝微粒体,分别加入17种中药,HPLC法测定大鼠肝微粒体中CYP2D6的探针药物右美沙芬(DM)的代谢率,通过代谢率降低的现象初步筛选出能抑制肝微粒体中CYP2D6代谢的药物。结果槲皮素、黄芩苷、厚朴提取物、清开灵注射液、盐酸川芎嗪注射液可明显降低DM的代谢率(P<0.01)。结论初步筛选出槲皮素、黄芩苷、厚朴提取物、清开灵注射液、盐酸川芎嗪注射液这5种中药可抑制肝微粒体CYP2D6酶活性。此方法可作为高通量筛选对CYP2D6活性有抑制作用中药的技术平台。Objective To screen the chemical components, extract, and injection, which have the inhibitory effect on cytochrome P4502D6 （CYP2D6） in liver microsomes of rats, from 17 kinds of Chinese materia medica （CMM） and develop a technical method for screening CMM possessed inhibitory effect on CYP2D6 in liver microsomes of rats by high throughout. Methods The liver microsomes of rats were incubated with 17 kinds of CMM at the presence of Dextromethorphan （DM）. DM Metabolic rate （DX/ DM, DX： Dextrophan, metabolites of DM） in liver microsomal reconstituted system was measured by HPLC and used as probe to determine the activity of CYP2D6. The inhibition of CMM on rat CYP2D6 was identified by decreasing the metabolic rate. Results Quercetin, baicalin, extract of Flos Magnollae Officinalis, Qingkailing Injection, and Tetramethylpytazine Hydrochloride Injection inhibited the DM metabolic rate （P〈0. 01）. Conclusion Five kinds of CMM have been obtained, they are quercetin, baicalin, extract of Flos Magnoliae Officinalis, Qingkailing Injection, and Tetramethylpytazine Hydrochloride Injection, which can inhibit the activity of CYP2D6 in liver microsomes of rats. The method mentioned above can be used as a useful technique to high throughout screening of CMM possessed the inhibitory effect on CYP2D6.

关 键 词：细胞色素P4502D6(CYP2D6) 肝微粒体 右美沙芬 

分 类 号：R285.5[医药卫生—中药学]