中国药理学与毒理学杂志2013，Vol.27Issue(1)：6-12,7.DOI:10.3867/j.issn.1000-3002.2013.01.002
注射用丹参总酚酸(冻干)对人CYP450酶和P-糖蛋白体外抑制作用及对大鼠CYP1A2和CYP3A体内诱导作用
Inhibitory effect of total salvianolate lyophilized injection, a herbal preparation, on human cytochrome P450 and P-glycoprotein in vitro and inductive effect on rat CYP1A2 and CYP3A in vivo
摘要
Abstract
OBJECTIVE To investigate the inhibitory effect of salvianolate lyophilized injection (SLI) on human cytochrome P450 (CYP450) and P-glycoprotein (P-gp) system in vitro and the inductive effect on rat CYP1A2 and CYP3A in vivo.METHODS ① IC50 of cytochrome P-4501A2 (CYP1A2.),CYP2Cg,CYP2C19,CYP2D6 and CYP3A4 inhibitors was evaluated by chemiluminescence using P450-GloTM Screening Systems.The inhibition on CYP450 in vitro from SLI was evaluated by IC50.② Wistar rats were sc given SLI 3,10 and 30 mg·kg-1 or inducer.The method of probe substrate was used for evaluating the induction of rat CYP1A2 and CYP3A from SLI by comparing the production rate of metabolites.③ The ATPase activities of SLI were determined by ATPase assay kit,which can evaluate whether SLI is a substrate or inhibitor of P-gp.RESULTS ① IC50 of inhibitors and SLI was compared (CYP1A2,0.012 μmol·L-1 vs840 μmol·L-1 ; CYP2Cg,3.362 μmol·L-1 vs704 μmol·L-1 ; CYP2C19,3.236 μmol·L-1 vs 306 μmol·L-1 ; CYP2D6,0.117 μmol·L-1 vs 2660 μmol·L-1 ; and CYP3A4,0.078 μmol·L-1 vs 1780 μmol·L-1).② Compared with control group (86.4 ±6.3)nrnol·g-1 ·min-1,the activities of rat CYP1A2 in SLI 3,10 and 30 mg·kg-1 groups were 83.3 ±6.6,82.5 ±4.0 and (83.4 ±6.6)μmol·g-1 ·min-1,respectively.Compared with control group (16.1 ±0.9)nmol·g-1 ·min-1,the activities of rat CYP3A in SLI 3,10 and 30 mg·kg-1 groups were 15.9 ±1.0,15.9±0.7 and (15.7 ±0.6)nmol·g-1 ·min-1 (P＜0.05).③ ATPase activity of SLI 0.0002,0.0006,0.0002,0.005,0.017,0.052,0.156 and 0.468 g·L-1 according to the clinical human blood-drug level was compared with that in control group,respectively (5.8,5.3,5.8,5.5,5.8,5.2,5.8,and 5.3 vs 5.8 μmol · g-1 · min-1),but there was no significant difference.CONCLUSION SLI may neither induce rat CYP1A2 or CYP3A in vivo,nor inhibit human CYP1A2,CYP2C9,CYP2C19,CYP2D6 and CYP3A4 in vitro.It is not a potential substrate or inhibitor for human P-gp in vitro.关键词
注射用丹参总酚酸(冻干)/P-糖蛋白/细胞色素P450 CYP1A2/细胞色素P450 CYP3AKey words
salvianolate lyophilized injection/P-glycoprotein/cytochrome P-450 CYP1A2/cytochrome P-450 CYP3A分类
医药卫生引用本文复制引用
胡冰,段超慧,岳洁浩,马英丽,周大铮,李德坤,叶正良..注射用丹参总酚酸(冻干)对人CYP450酶和P-糖蛋白体外抑制作用及对大鼠CYP1A2和CYP3A体内诱导作用[J].中国药理学与毒理学杂志,2013,27(1):6-12,7.基金项目
The project supported by National Science and Technology Major Project of China (2012ZX09101202) （2012ZX09101202）
国家科技重大专项资助项目(2012ZX09101202) （2012ZX09101202）
