戊己丸不同配比方对大鼠体外CYP3A1/3A2酶活性的影响  

Effects of Wuji pill compound with different compatibility on cytochrome P450 CYP3A1/3A2 in rat liver microsomes in vitro

作　　者：翁小刚[1] 李玉洁[1] 杨庆[1] 王怡薇[1] 刘晓霓[1] 韩晓[1] 张甘霖[2] 隋峰[1] 朱晓新[1] 梁日欣[1] 

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]北京中医药大学,北京100029

出　　处：《中国中药杂志》2010年第9期1164-1169,共6页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(30930114);国家"十一五"科技支撑计划项目子课题(2006BAI08B04-4);国家自然科学基金重大研究计划项目(90709017);国家中医药管理局中医药行业科研专项(2008070036);中国中医科学院自主选题(ZZ2006102)

摘　　要：目的:研究戊己丸不同配比方对大鼠体外肝微粒体CYP3A1/3A2酶活性的影响,从"中药配伍-代谢"关系探讨戊己丸的配伍机制。方法:按L9(34)正交表,戊己丸的配比设计为9个受试复方,以睾丸酮为探针药,HPLC检测戊己丸对大鼠体外肝微粒体CYP3A1/3A2酶活性的影响。结果:黄连、吴茱萸、白芍各提取物及戊己丸1号～9号方抑制CYP3A1/3A2的IC50分别为38.96,871.96,15519.17,43.17,60.47,276.12,133.40,118.08,88.47,64.36,35.13,39.91mg.L-1;黄连及戊己丸均可显著抑制CYP3A1/3A2酶活性,不同配比戊己丸抑制CYP3A1/3A2酶活性作用不同,有统计学差异;随着黄连在戊己丸方中剂量水平的增高,戊己丸组方抑制CYP3A1/3A2酶活性的能力增强,且戊己丸组方中吴茱萸和白芍配比不同可以影响方中黄连抑制CYP3A1/3A2酶活性的程度。结论:戊己丸配比不同,对CYP3A1/3A2酶活性的抑制作用不同,这种差异可能是不同配比戊己丸药效学、药动学差异的原因所在。Objective： Wuji pill is a prescription of traditional Chinese medicine（TCM） and was composed of Rhizoma Coptidis, Fructus Evodiae Rutaeearpae and Radix Paeoniae Alba. The aim of this research is to investigate the effects of Wuji pill compound with different compatibility on the levels of enzymic activity of cytochrome P450 CYP3A1/3A2 in rat liver microsomes in vitro, and to confirm the compatibility mechanism of Wuji pill from the point of relationships between compound prescription of TCM and metabolism. Method： With testosterone being a probe, the levels of enzymic activity of CYP3A1/3A2 were detected by HPLC, which were suppressed by Wuji pill with different compatibility in vitro. Result： The IC50 of Rhizoma Coptidis, Fruetus Evodiae Rutaeearpae, Radix Paeoniae Alba and 1#-9# of different level Wuji pill is： 38.96, 871.96, 15 519. 17, 43.17, 60. 47, 276. 12, 133.40, 118.08, 88.47, 64. 36, 35.13 and 39. 91 mg · L^-1 , respectively. Rhizoma Coptidis and 1#-9# of Wuji pill can suppress the enzymic activity of CYP3A1/3A2 significantly, and the capability of Rhizoma Coptidis in Wuji pill of action on CYP3A1/3A2 can be modified by different composition of Fruetus Evodiae Rutaeearpae and Radix Paeoniae in Wuji pill, and there are statistical differences among the IC50 of 1#- 9# of Wuji pill. While the ratio of Rhizoma Coptidis raises up in Wuji pill, Wuji pill may suppress the enzymic activity of CYP1A2 largely. Conclusion： The reason why Wuji pill with different compatibility has different pharmaeodynamics and pharmacokinetics characteristics is likely to lie in the difference of the capability of Wuji pill with different compatibility on CYP3A1/3A2.

关 键 词：戊己丸 CYP3A1/3a2 睾丸酮 HPLC 中药配伍 

分 类 号：R285.5[医药卫生—中药学]