稳心颗粒对大鼠细胞色素P450酶的影响

摘要

目的 用cocktail探针药物法评价稳心颗粒对大鼠体内CYP1 A2,CYP2C9,CYP2C19,CYP2D6,CYP2EI和CYP3A4亚型酶活性的影响.方法 雄性Wistar大鼠随机分为稳心颗粒高、低剂量组和空白对照组.稳心颗粒高、低剂量组灌胃给予稳心颗粒,空白对照组灌胃给予0.9％氯化钠溶液,连续7d.第8天腹腔注射探针药物咖啡因、甲苯磺丁脲、奥美拉唑、美托洛尔、氯唑沙宗和氨苯砜.尾静脉取血,用高效液相色谱法检测血样,比较药动学参数变化.结果 高、低剂量稳心颗粒分别使咖啡因的AUC(0-∞)增加1.635倍和1.435倍,分别使氨苯砜的AUC(0-∞)增加1.816倍和1.324倍.高剂量稳心颗粒使奥美拉唑和氯唑沙宗的AUC(0-∞)增加2.748倍和1.696倍.结论 高剂量稳心颗粒对CYP2C19和CYP2E1活性有弱抑制作用,稳心颗粒对CYP1 A2和CYP3 A4的活性有弱抑制作用.%Objective To investigate the effect of wenxin, granu!e( WXG) on the activity of CYP1A2,2C9,2C19,2D6, 2E1 and CYP3A4 by cocktail probe drugs in rats. Methods The male Wistar rats were divided randomly into the high-dose group, low-dose group, which were treated by intragastric injection with WXG, and blank control group which was administrated by intragastric injection with 0. 9% sodium chloride solution, for seven days. Cocktail probe drugs as caffeine, tolbutamide, omeprazole, meloprolol, chlorzoxazone and dapsone were administrated by intraperitoneal injection on the eighth day. Then, plasma was obtained from the caudal vein, and the blood samples were analyzed by HPLC. The pharmaeokinetie parameters of both high-dose and low-dose groups were compared with the control group. Results The AUC(0-ω) of caffeine was increased 1.635-fold and l.43S-fold by the high-dose and low-dose of WXG, respectively while that of dapsone was raised 1,816-fold and 1.324-fold, respectively. Furthermore,the AUC(0-ω) of omeprazole and chlorzoxazone were increased 2. 748-fold and 1.696-fold by the high dose of WXG,respectively. Conclusion Our study suggests that the high-dose of WXG has the potential to inhibit the activity of CYP2C19, CYP2E1, CYP1A2 and CYP 3A4.