甘草-大戟配伍对大鼠肝药酶亚型CYP1A2、CYP2E1和CYP3A4活性的影响  

Effect of Glycyrrhizae Radix and Euphorbiae Pekinensis Radix compatibility on activities of CYP1A2,CYP2E1 and CYP3A4 from rat liver microsomes

作　　者：张奉献 乔姗姗 王莎 徐风[2] 王如峰 ZHANG Feng-xian;QIAO Shan-shan;WANG Sha;XU Feng;WANG Ru-feng(School of Life Sciences,Beijing University of Chinese Medicine,Beijing 102488;School of Pharmaceutical Sciences,Peking University,Beijing 100080)

机构地区：[1]北京中医药大学生命科学学院,北京102488 [2]北京大学药学院,北京100080

出　　处：《中南药学》2025年第3期581-586,共6页Central South Pharmacy

基　　金：国家科技重大专项(No.2019ZX09201004-002)。

摘　　要：目的研究甘草、大戟药对配伍前后对大鼠肝药酶亚型CYP1A2、CYP2E1和CYP3A4活性的影响。方法采用Cocktail探针药物法测定甘草-大戟配伍对探针药物非那西丁、氯唑沙宗和氨苯砜代谢的影响,评价其对大鼠肝药酶亚型CYP1A2、CYP2E1和CYP3A4活性的影响。结果甘草与大戟配伍后,与空白对照组相比,甘草-大戟1∶1组:非那西丁的半衰期(t_(1/2))与表观分布容积(V_(d))显著增大,曲线下面积(AUC)显著减小、氯唑沙宗清除率(CL)与V_(d)显著减小,AUC显著增大、氨苯砜的AUC显著减小;甘草-大戟2∶1组:非那西丁的t_(1/2)与AUC显著减小、氯唑沙宗的CL与V_(d)显著减小,AUC显著增大、氨苯砜的V_(d)显著减小;甘草-大戟3∶1组:非那西丁的t_(1/2)与V_(d)显著减小,CL显著增大、氯唑沙宗的t_(1/2)与AUC显著增大,CL与V_(d)显著减小、氨苯砜的CL与V_(d)显著减小,AUC显著增大。结论甘草-大戟1∶1配伍对CYP1A2和CYP2E1有抑制作用,而对CYP3A4有促进作用;甘草-大戟2∶1和3∶1配伍对CYP1A2有显著促进作用,对CYP2E1和CYP3A4有抑制作用,这可能是其配伍禁忌的内在机制之一。Objective To determine the effect of Glycyrrhizae Radix(GR)and Euphorbiae Pekinensis Radix(EPR)on activities of CYP1A2,CYP2E1 and CYP3A4 from rat liver microsomes before and after the compatibination use.Methods The effect of GR and EPR combination on the metabolism of the probe drugs phenacetin,chlorzoxazone and dapsone was determined by Cocktail probe drug method.Their effects on the activity of CYP1A2,CYP2E1 and CYP3A4 subtypes of liver drug enzymes in rats were evaluated.Results The half-life(t_(1/2)),apparent volume of distribution(V_(d)),area under the curve(AUC)and clearance rate(CL)of the probes in the combination groups of GR and EPR were compared with those in the blank control group.In the GR-EPR(1∶1)group,the t_(1/2) and V_(d) of phenacetin increased while the AUC decreased obviously;the CL and V_(d) of chlorzoxazone decreased while the AUC increased obviously;and the AUC of dapsone decreased.In the GR-EPR(2∶1)group,the t_(1/2) and AUC of phenacetin decreased substantially;the CL and V_(d) of chlorzoxazone decreased while the AUC increased substantially;the V_(d) of dapsone decreased obviously.In the GR-EPR(3∶1)group,the t_(1/2) and V_(d) of phenacetin decreased while the CL increased greatly;the t_(1/2) and AUC of chlorzoxazone increased while the CL and V_(d) decreased greatly;the CL and V_(d) of dapsone decreased while the AUC increased greatly.Conclusion GR∶EPR(1∶1)combination inhibits the activity of CYP1A2 and CYP2E1 but promotes CYP3A4,while GR∶EPR(2∶1)and(3∶1)significantly promote the activity of CYP1A2 and inhibit CYP2E1 and CYP3A4.This may be a possible mechanism of combination incompatibility.

关 键 词：十八反 甘草 大戟 CYP1A2 CYP2E1 CYP3A4 

分 类 号：R286[医药卫生—中药学]