金铃子散不同配比方对大鼠肝药酶CYP450 3A4活性的影响  

Influence of Jinglingzi Powder with Different Compatibility on the Activity of Cytochrome P450 3A4 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：《中国实验方剂学杂志》2011年第22期117-122,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家中医药管理局中医药行业科研专项(200807036)

摘　　要：目的:通过比较金铃子散不同配比方对肝细胞色素P450 3A4(cytochrome P450 3A4,简称CYP 3A4)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微粒体孵育体系,测定不同配比方对CYP 3A4的半数抑制浓度(IC50);体内实验采用大鼠,口服给予金铃子散不同配比方5 d后注射探针药物睾酮,通过微透析探针采集肝脏部位样品,HPLC测定6-β-羟基-睾酮和原型物睾酮浓度,二者浓度之比作为CYP 3A4酶活性指标。结果:川楝子、延胡索单味提取物和配比方1～9体外对肝药酶CYP 3A4的IC50分别为(2.59±0.33),(0.87±0.30),(1.14±0.20),(1.00±0.13),(1.19±0.10),(2.33±0.15),(1.39±0.19),(1.14±0.20),(1.29±0.14),(1.43±0.32),(1.49±0.28)mg.L-1;体内实验结果显示:与正常对照组比较,金铃子散不同配比方、川楝子和延胡索单味提取物处理组大鼠CYP 3A4的酶活性均降低,金铃子散配比方抑制CYP 3A4酶活性的强弱顺序:方1(方4)>方7>方2(方5)>方8>方3>方9。结论:不同配比方对CYP 3A4酶的活性均有影响,川楝子和延胡索配伍显示出协同抑制作用。Objective： To illustrate the compatibility of Jinglingizi powder by investigating the influence of Jinglingzi powder with different compatibility on the enzymatic activity of cytochrome P450 3A4（CYP 3A4） from rat liver microsome.Method：The different compatibility of Jinglingizi powder was designed based on the orthogonal array L9（34）.In vitro test,rat liver microsome incubation system was applied to detect the 50% inhibitory concentration of Jinglingzi powder with different compatibility.In vivo experiment,rats were administered orally with the different compatibility of Jinglingizi powder（dose： 9.75 g·kg-1） from day 1 to day 5,then injected probe drug testosterone.The biosamples from liver tissue were obtained by microdialysis probe,then to be analysed by HPLC.The concentration of 6-β-testosterone and testosterone were accurately determined.The ratio hepatic concentration of 6-β-testosterone to hepatic concentration of testosterone,was applied to describe the CYP 3A4 enzyme activity.Result： The half maximal inhibitory concentrations（IC50） of the extract of Toosendan fruit,Rhizoma Corydalis and Jinlingzi Powder（formula.1-9） on the enzymatic activity of CYP3A4 were（2.59±0.33）,（0.87±0.30）,（1.14±0.20）,（1.00±0.13）,（1.19±0.10）,（2.33±0.15）,（1.39±0.19）,（1.14±0.20）,（1.29±0.14）,（1.43±0.32）,（1.49±0.28） mg·L-1,respectively.In vivo test,the CYP3A4 enzyme activity was inhibited by the different compatibility of Jinglingizi powder,compared with the normal control group.The inhibited intensity of Jinglingizi powde followed the order： formula 1（formula 4） formula 7 formula 2（formula 5） formula 8 formula 3 formula 9.Conclusion： The CYP3A4 enzyme activity is inhibited by the different compatibility of Jinglingizi powder,compared with the normal control group.Compatibility of Jinglingizi powder synergetically down-regulate the the CYP3A4 enzyme activity.

关 键 词：金铃子散 细胞色素P4503A4 中药配伍 微透析 

分 类 号：R285.5[医药卫生—中药学]