鸡尾酒法评价猫人参对大鼠细胞色素450酶活力的影响  

Evaluation on Actinidia valvata Dunn’s effect on CYP450 enzyme activity in rats by cocktail method

作　　者：涂安娜 林崇良[1] 鲍曦 温从丛 王贤亲 TU An-na;LIN Chong-liang;BAO Xi;WEN Cong-cong;WANG Xian-qin(Department of Pharmacy,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang 325035,China;不详)

机构地区：[1]温州医科大学附属第一医院药学部,浙江温州325035 [2]温州医科大学分析测试中心,浙江温州325035 [3]温州医科大学司法鉴定中心,浙江温州325000

出　　处：《中国卫生检验杂志》2021年第16期1985-1990,共6页Chinese Journal of Health Laboratory Technology

摘　　要：目的运用鸡尾酒法评估猫人参对大鼠CYP450酶活性(CYP2B1、CYP2D1、CYP3A2、CYP1A2、CYP2C11)影响。方法 24只大鼠随机分成猫人参低、中、高3组和对照组。猫人参组给予大鼠猫人参煎煮液(0.15 g/ml),低剂量组0.5 ml/只,中剂量组1.0 ml/只,高剂量组2.0 ml/只,对照组给予大鼠生理盐水2 ml/kg,持续给药30 d。30 d以后,4组灌胃给予大鼠5种探针药物,采集血浆样品,后用UPLC-MS/MS检测血浆中探针药及其代谢产物的浓度。结果与对照组对比,猫人参低中高3组的安非他酮的AUC都有升高(P <0.05),CL降低(P <0.05),高剂量组的美托洛尔AUC升高(P <0.05)、CL降低(P <0.05),低剂量组羟基美托洛尔的CL降低(P <0.05),低剂量组和高剂量组的甲苯磺丁脲AUC升高(P <0.05),参高剂量组的非那西汀AUC降低(P <0.05)。结论连续30 d大鼠灌胃猫人参,说明可能稍有抑制大鼠CYP2B1、CYP2D1和CYP2C9酶活性,稍有诱导大鼠CYP1A2酶活性的作用。Objective To evaluate the effects of Actinidia valvata Dunn on CYP450 enzyme activity( CYP2 B1,CYP2 D1,CYP3 A2,CYP1 A2,CYP2 C11) in rats using the cocktail method. Methods Twenty four rats were randomly divided into 3 Actinidia valvata Dunn groups( high,medium and low-dose) and control group. 0. 15 g/ml was given to rats in Actinidia valvata Dunn groups,0. 5 ml/rat in low-dose group,1. 0 ml/rat in medium-dose group,2. 0 ml/rat in high-dose group;2 ml/kg normal saline was given to rats in control group for 30 days. After 30 days,rats in 4 groups were given 5 kinds of probe drugs by intragastolic administration. Plasma samples were collected,and the concentrations of probe drugs and their metabolites in plasma were detected by UPLC-MS/MS. Results Compared with the control group,the AUC of bupropion in the low,middle and high Actinidia valvata Dunn groups all increased( P < 0. 05) and the CL decreased( P < 0. 05). The AUC of metoprolol in the high-dose Actinidiavalvata group increased( P < 0. 05) and the CL decreased( P < 0. 05). The CL of hydroxymetoprolol was lower in the low-dose group( P < 0. 05). The AUC of tolbutamide in low-dose and high-dose groups increased( P < 0. 05). The AUC of phenacetin in the high-dose group was reduced( P < 0. 05). Conclusion Actinidia valvata Dunn was administered to rats for 30 consecutive days,indicating that it may slightly inhibit the CYP2 B1,CYP2 D1 and CYP2 C9 enzyme activities in rats,and slightly induce the CYP1 A2 enzyme activities in rats.

关 键 词：超高效液相色谱-串联质谱 探针药 猫人参 CYP2B1 CYP2D1 CYP2C9 

分 类 号：O657[理学—分析化学]