川乌配伍半夏对大鼠CYP3A的影响  

Influence of Compatibility of Aconiti Radix and Pinelliae Rhizoma on CYP3A in Rats

作　　者：陈红[1] 程再兴[1,2] 吴锦俊[2] 林娜[1,2] 

机构地区：[1]福建中医药大学药学院,福州350122 [2]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》2017年第2期75-80,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点基础研究发展计划(973计划)项目(2011CB505300;2011CB505305);福建中医药大学校管课题(XB2011005);国家教育部与国家中医药管理局科技基础性工作专项(2014FY111100-5)

摘　　要：目的:研究川乌配伍半夏对大鼠细胞色素P450酶系(CYP)3A1/2的影响,从CYP介导的代谢性相互作用角度阐述"十八反"中半夏反乌头的科学内涵。方法:采用体外温孵法和体内探针法检测CYP3A活性,采用免疫印迹试验(Western blot)和荧光定量聚合酶链式反应技术检测蛋白和mRNA表达。结果:与生/制川乌配生半夏对应剂量组相比,生/制川乌配法/姜半夏组6β-羟基睾酮(6β-OH-Tes)生成速率显著降低;生川乌配法/姜半夏组的CYP3A蛋白表达明显降低,制川乌配法/姜半夏仅部分剂量组明显降低;生川乌配法/姜半夏在0.6和1.2 g·kg-1剂量组CYP3A1 mRNA表达显著增加,制川乌配法/姜半夏在0.60 g·kg-1剂量组CYP3A1 mRNA表达显著降低。与生川乌配生/法/姜半夏对应剂量组相比,制川乌配生/法/姜半夏组6β-OH-Tes生成速率亦多显著降低;制川乌配生/法半夏组CYP3A蛋白表达明显降低;制川乌配生/法/姜半夏组CYP3A1 mRNA表达呈增加趋势。与生川乌配生半夏组相比,配伍法半夏后6'-羟基丁螺环酮(6'-OH-BP)和丁螺环酮(BP)的药时曲线下面积(AUC0-t)比值(6'-OH-BP/BP),1-(2-嘧啶基)哌嗪(1-PP)与BP的AUC0-t比值(1-PP/BP)均增加,而配伍姜半夏后二者生成未发生变化;与制川乌配生半夏相比,配伍法/姜半夏后6'-OH-BP/BP均减小,而1-PP/BP均未变。结论:配生/法/姜半夏后均可逆转生/制川乌对大鼠CYP3A的抑制作用,可加快川乌中相应成分的代谢,起到降毒或减效作用。Objective： The aim of the article was to explore the compatibility connotation of Aconiti Radix and Pinelliae Rhizoma from cytochrome P450 enzyme system（ CYP） 3A1 /2 mediating metabolic herb-herbs interaction in rats. Method： Incubation in vitro and probe method in vivo were used to detect the activity of CYP3 A. The fluorescence quantitative polymerase chain reaction（ PCR） technology and Western blot were applied to determine expression of mRNA and protein. Result： Compared with unprocessed Aconiti Radix（ RAR） /Aconiti Radix Cocta（ ARC）-unprocessed Pinelliae Rhizoma（ UPR）, the production rate of 6β-hydroxytestosterone（ 6β-OH-Tes） and the expression of CYP3 A protein were all decreased in RAR-Pinelliae Rhizoma Praeparatum（ PRP） / Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine（ PRPZA）, but partial dose group of ARC-PRP / PRPZA was significantly decreased. The expression of CYP3A1 mRNA were increased in 0. 6,1. 2 g·kg^- 1 groups of RAR-PRP / PRPZA as well as decreased in 0. 6 g·kg^- 1group of ARC-PRP / PRPZA.Compared with the corresponding dose group of RAR-UPR / PRP / PRPZA,the production rates of 6β-OH-Tes were most significantly reduced and the expression of CYP3 A protein of ARC-UPR / PRP were decreased, while the expression of CYP3A1 mRNA were increased in most groups of ARC-UPR / PRP / PRPZA. The rates of 6＇-hydroxybuspirone（ 6＇-OH-BP） / buspirone（ BP）（ AUC0-tof 6＇-OH-BP / AUC0-tof BP） and 1-（ 2-pyrimidinyl）-piperazine（ 1-PP） / BP（ AUC0-tof 1-PP / AUC0-tof BP） were all increased in RAR-PRP as well as did not change in RAR-PRPZA by comparing with RAR-UPR. The rates of 6＇-OH-BP / BP were all decreased and the rates of1-PP / BP did not change in ARC-PRP / PRPZA by comparing with ARC-UPR. Conclusion： Inhibition of RAR / ARC on CYP3 A activity can be reversed by compatibility with UPR / PRP / PRPZA,which may accelerate the metabolism of some components in RAR / ARC,then the toxicity or the pharmacological action of RAR / ARC is we

关 键 词：十八反 睾酮 mRNA 丁螺环酮 1-(2-嘧啶基)哌嗪 川乌 半夏 

分 类 号：R969.1[医药卫生—药理学] R289[医药卫生—药学]