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目的:用Cocktail探针药物法,研究黄柏不同炮制品对大鼠细胞色素P450酶(CYP450)4种亚型活性的影响并进行比较,探讨黄柏的炮制原理。方法:将SD大鼠随机分组,生、酒、盐黄柏组分别灌胃生、酒、盐黄柏水煎液(3.24 g/kg),空白对照组灌胃生理盐水,灌胃1 w,于第8天给予由茶碱、氨苯砜、氯唑沙宗、甲苯磺丁脲组成的混合探针药物,在不同时间点采集血样,利用HPLC检测探针药物在大鼠体内的代谢情况,通过DAS3.0软件计算各探针药物的药动学参数并进行统计分析,以评价生、制黄柏对CYP450酶的影响。结果:与空白对照组比较,生品组和盐品组茶碱的t_(1/2)均显著增加,生品组和酒品组的CL/F均显著降低,AUC_(0-t)、AUC_(0-∞)均显著增加;生品组、酒品组和盐品组氨苯砜的t_(1/2)、AUC_(0-t)、AUC_(0-∞)均显著降低,CL/F显著增加;生品组和盐品组氯唑沙宗的AUC_(0-t)显著增加,酒品组氯唑沙宗的t_(1/2)、AUC_(0-∞)、AUC_(0-t)均显著降低,CL/F显著增加;生品组、酒品组和盐品组甲苯磺丁脲的AUC0-t均显著降低。结论:生黄柏对CYP1A2具有抑制作用,对CYP3A4具有诱导作用,对CYP2C9、CYP2E1活性的影响有待进一步的研究,而经炮制成为酒黄柏和盐黄柏后可改变药物代谢酶的活性;酒黄柏可降低对CYP1A2的抑制作用和增强对CYP3A4的诱导作用,该研究可为解释酒制黄柏能缓和药性提供参考依据。
OBJECTIVE: To study the effect of different processed products of Cortex Phellodendri on the activities of four subtypes of cytochrome P450 enzyme (CYP450) in rats by Cocktail probe drug method and to compare the processing principle of Treats. Methods: SD rats were randomly divided into three groups: raw, alcohol and salt cork decoction (3.24 g / kg) respectively. The blank control group was given gavage with normal saline for 1 w, 8 days given by theophylline, dapsone, chlorzoxazone, tolbutamide mixed probe drugs, blood samples were collected at different time points, the use of HPLC to detect probe drug metabolism in rats by DAS3 .0 software to calculate the pharmacokinetic parameters of each probe drug and statistical analysis to evaluate the impact of Health and Cork on CYP450 enzyme. Results: Compared with the blank control group, the t_ (1/2) of theophylline of the raw product group and the saline group increased significantly, while the CL / F of the raw product group and the wine group decreased significantly. The AUC_ (0-t), AUC_ (0-∞) were significantly increased. The d_ (1/2), AUC_ (0-t) and AUC_ (0_∞) of dapsone in raw product group, / F increased significantly; the AUC_ (0-t) of chlorzoxazone in raw product group and salt group increased significantly, t_ (1/2), AUC_ (0_∞), AUC_ 0-t) were significantly lower, CL / F significantly increased; raw product group, wine group and salt group tolbutamide urea AUC0-t were significantly lower. CONCLUSION: Phellodendron chinense has inhibitory effect on CYP1A2 and CYP3A4, and its effect on the activities of CYP2C9 and CYP2E1 remains to be further studied. However, the activity of drug metabolizing enzymes can be changed after being processed into wine cork and salt cork; cork down On CYP1A2 inhibition and enhance the induction of CYP3A4, this study may provide a reference for the interpretation of wine cork can ease the drug.