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。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 Chinesemateria medica(CMM)and develop a technical method for screening CMM possessed inhibitory effect onCYP2D6 in liver microsomes of rats by high throughout.Methods The liver microsomes of rats wereincubated with 1 7 kinds of CMMat the presence of Dextro methorphan(DM).DM Metabolic rate(DX/DM,DX:Dextrophan,metabolites of DM)in liver micros omal reconstituted system was measured byHPLC and used as probe to determine the activity of CYP2D6.The inhibition of CMM on rat CYP2D6 wasidentified by decreasing the metabolic rate.Results Quercetin,baicalin,extract ofFlos MagnoliaeOfficinalis,Qingkailing Injection,and Tetramethylpytazine Hydrochloride Injection inhibited the DMmetabolic rate (P<0.01).Conclusion Five kinds of CMM have been obtained,they are quercetin,bai calin,extract of F tos Magnoliae Officinalis,Qingkailing Injection,and Tetra methyl pytazineHvdrochloride Injection,which can inhibit the activity of CYP2D6 in liver micro somes of rats.The methodmentioned above can be used as a useful technique to high throu ghout screening of CMM possessed theinhibitory effect on CYP2D6.

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