复方丹参滴丸对大鼠肝细胞色素P450酶的影响  

Effect of compound Danshen Dripping Pills on rat hepatic cytochrome P450

作　　者：胡东华[1,2] 王宇光[2] 陈志武[1] 马增春[2] 梁乾德[2] 肖成荣[2] 谭洪玲[2] 汤响林[2] 李桦[3] 沈国林[3] 张伯礼[4] 高月[2] 

机构地区：[1]安徽医科大学药理学教研室,安徽合肥230032 [2]军事医学科学院放射医学研究所药理毒理研究室,北京100850 [3]军事医学科学院毒物药物研究所药物代谢研究室,北京100850 [4]天津中医药大学现代中药国家重点实验室,天津300193

出　　处：《中国药理学与毒理学杂志》2013年第4期678-684,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：国家重点基础研究发展计划(2012CB518402)~~

摘　　要：目的观察复方丹参滴丸及其单味药对大鼠肝细胞色素P450酶(CYP)主要亚型的影响。方法 SD大鼠分别ig给予复方丹参滴丸0.3258 g.kg-1,丹参0.27 g.kg-1,三七0.0528 g.kg-1和冰片0.003 g.kg-1,每天1次,连续28 d,取大鼠肝微粒体,与CYP1A2,CYP2B6,CYP2C12,CYP2C13,CYP2D2和CYP3A1特异性底物探针共孵育,用高效液相色谱-质谱联用仪(HPLC-MS/MS)测定底物的代谢产物,分析CYP1A2,CYP2B6,CYP2C12,CYP2C13,CYP2D2和CYP3A1酶活性,同时用PCR方法检测cyp1a2,cyp2b1/2,cyp2c11,cyp2e1和cyp3a1 mRNA表达的变化。结果与正常对照组相比,苯巴比妥(阳性对照)对CYP2D2和CYP3A1活性有明显抑制作用,对CYP1A2,CYP2B6,CYP2C12和CYP2C13有明显诱导作用(P<0.05,P<0.01);复方丹参滴丸对CYP1A2和CYP2B6活性有明显抑制作用,对CYP2D2有诱导作用(P<0.05);丹参对CYP1A2和CYP2B6活性有明显抑制作用(P<0.05);三七对CYP1A2,CYP2B6,CYP2C13和CYP2D2活性有明显抑制作用(P<0.05);冰片明显抑制CYP1A2,CYP2B6,CYP2C12,CYP2C13和CYP2D2活性(P<0.01),且抑制强度高于复方丹参滴丸。与正常对照组相比,苯巴比妥对cyp1a2和cyp2b1/2 mRNA水平有明显诱导作用(P<0.05);复方丹参滴丸、丹参和三七对cyp1a2,cyp2b1/2,cyp2c11,cyp2e1和cyp3a1 mRNA水平无明显影响;冰片对cyp1a2,cyp2b1/2和cyp2c11 mRNA水平有明显抑制作用(P<0.05,P<0.01)。结论复方丹参滴丸中各单味药对CYP酶的影响强于全方对CYP酶的影响,其中以冰片对药物代谢酶的影响最为显著。OBJECTIVE To observe the inductive effect of compound Danshen Dripping Pills（CDDP） on main subtypes of rat hepatic cytochrome P450（CYP）.METHODS Male SD rats were ig given CDDP 0.3258 g·kg-1,Radix Salviae Miltiorrhizae（RSM） 0.27 g·kg-1,Radix Notoginseng 0.0528 g·kg-1 and Borneolum Syntheticum（BS） 0.003 g·kg-1,once daily,for 28 d.Then the rat liver microsomes were cultured with probe drugs for CYP.Activities of CYP1A2,CYP2B6,CYP2C12,CYP2C13,CYP2D2 and CYP3A1 were determined by high-performance liquid chromatography-mass spectrometry（HPLC/MS/MS）.The expression of cyp1a2,cyp2b1/2,cyp2c11,cyp2e1 and cyp3a1 mRNA was determined by RT-PCR.RESULTS Compared with normal control group,phenobarbitone（positive control） had inhibitory effect on the enzyme activity of CYP2D2 and CYP3A1,while the activities of CYP1A1,CYP2B6,CYP2C12 and CYP2C13 were induced（P0.05）.CDDP inhibited the activity of CYP1A2 and CYP2B6,but induced CYP2D2（P0.05）.RSM inhibited the activities of CYP1A2 and CYP2B6（P0.05） while Radix Notoginseng inhibited CYP1A2,CYP2B6,CYP2C13 and CYP2D2（P0.05）.BS had inhibitory effect on CYP1A2,CYP2B6,CYP2C12,CYP2C13 and CYP2D2（P0.01）.On the mRNA level,compared with normal control group,phenobarbitone had inductive effect on cyp1a2 and cyp2b1/2 mRNA（P0.05）;CDDP,RSM and Radix Notoginseng had no significant effects on the mRNA level of cyp1a2,cyp2b1/2,cyp2c11,cyp2e1 and cyp3a1.BS significantly inhibited the mRNA level of cyp1a2,cyp2b1/2 and cyp2c11（P0.05,P0.01）.CONCLUSION A single drug has more significant effect on enzymes than CDDP.BS has the most significant inhibitory effect on drug metabolic enzymes.

关 键 词：复方丹参滴丸 丹参 三七 冰片 细胞色素P450酶系统 

分 类 号：R285.5[医药卫生—中药学]