金铃子散不同配比方对大鼠肝药酶CYP1A2活性的影响  

Influence of Jinlingzi powder with different compatibility on activity of cytochrome P1A2 from rat liver microsomes

作　　者：成龙[1] 王岚[1] 王彦礼[1] 梁日欣[1] 杨伟鹏[1] 王伟[1] 胡楠[1] 殷小杰[1] 翁小刚[1] 王怡薇[1] 杨庆[1] 

机构地区：[1]中国中医科学院中药研究所,北京100700

出　　处：《中国中药杂志》2012年第5期648-653,共6页China Journal of Chinese Materia Medica

基　　金：国家中医药管理局中医药行业科研专项(200807036);国家自然基金青年科学基金项目(30801542)

摘　　要：目的:通过比较金铃子散不同配比方对大鼠肝药酶CYP1A2活性的影响,探讨其配伍规律。方法:按L9(34)正交表,设计9个不同配比组方。体外实验采用大鼠肝药酶孵育体系,测定不同配比方对CYP1A2的半数抑制浓度(IC50);体内实验采用大鼠口服金铃子散不同配比方5 d后注射探针药物非那西丁,通过微透析探针采集肝脏部位样品,HPLC测定非那西丁及其代谢物对乙酰氨基酚浓度,winNonlin软件统计拟合药代参数。结果:川楝子、延胡索单味提取物和配比方1～9对肝药酶CYP1A2的IC50分别为(0.025 2±0.005 2),(0.012 1±0.007 9),(0.091 9±0.015 0),(0.071 9±0.005 3),(0.028 2±0.004 5),(0.075 4±0.015 5),(0.062 8±0.003 3),(0.091 9±0.015 0),(0.197 6±0.027 3),(0.159 1±0.008 1),(0.131 1±0.008 5)g.L-1,无显著抑制酶CYP1A2活性。体内实验,药代参数显示金铃子散不同配比方均能诱导CYP1A2活性,影响酶活性强弱顺序是:诱导剂组(方3)>方4(方5)>方9(方6,方1,方2,方8,川楝子,延胡索组)>方7>正常对照组。结论:金铃子散不同配比方对肝药酶CYP1A2活性有诱导作用,且诱导作用的强弱与配比有一定的相关性。To illustrate the compability rule of Jinlingizi powder,by investigating the effects of Jinlingzi Powder with different compatibility on the enzymatic activity of cytochrome P1A2（CYP1A2） from rat liver microsome.The different compability of Jinlingizi powder is designed,based on the orthogonal array L9（34）.In vitro test,rat liver microsomes incubation system is applied to detect the 50% inhibitory concentraton of Jinlingzi powder with different compatibility to cytochrome P1A2（CYP1A2） enzyme.In vivo experiments,rats is treated orally with the different compability of Jinlingizi powder for 5 days,then be injected with probe drug phenacetin.The biosample from liver tissue is obtained by microdialysis probe,then analysisd by HPLC.The concentration-time data are modulated by software WinNonlin.IC50 data show no significant inhibitory activty to cytochrome P1A2.Acetaminophen and phenacetin PK parameters indicate that the different compability of Jinlingizi powder can modulate the CYP 1A2 mediated metabolism,which is associate with the compatibility of Jinlingzi powder.

关 键 词：金铃子散 中药配伍 CYP1A2 半数抑制浓度 微透析 

分 类 号：R285.5[医药卫生—中药学]