左归饮水提物对大鼠Cyp2b1、Cyp2c11、Cyp2c7亚酶活性的影响  

Effect of Water Extract of Zuogui Decoction on the Activities of Metabolic Enzymes Cyp2b1,Cyp2c11,and Cyp2c7 in Rats

作　　者：洪世忠 施哲媛 何帆 张盛[1] 陈卫东[1] HONG Shi-zhong;SHI Zhe-yuan;HE Fan;ZHANG Sheng;CHEN Wei-dong(Anhui University of Chinese Medicine,Anhui Hefei 230012,China)

机构地区：[1]安徽中医药大学,安徽合肥230012

出　　处：《安徽中医药大学学报》2018年第4期59-64,共6页Journal of Anhui University of Chinese Medicine

基　　金：安徽高校自然科学研究项目(KJ2017A297)

摘　　要：目的采用Cocktail探针药物法评价左归饮对大鼠体内细胞色素氧化酶P450亚型酶Cyp2b1、Cyp2c11和Cyp2c7代谢活性的影响,为左归饮的开发应用提供实验依据。方法选用阿莫地喹、安非他酮、奥美拉唑分别作为Cyp2b1、Cyp2c11和Cyp2c7的探针底物,制备成Cocktail混合溶液。将SD雄性大鼠分为实验组和空白组,实验组每日清晨灌服高、中、低剂量左归饮溶液,空白组每日清晨灌服空白溶剂,均连续给药14d。第14天清晨尾静脉注射混合探针药物后于各时间点测定大鼠体内探针药物的血药浓度。经DAS 2.0软件计算探针药物的药物代谢动力学参数,评价左归饮对大鼠体内代谢酶活性的影响。采用LCMS/MS法同时测定3种探针药物的血药浓度。结果与空白组比较,高、中、低剂量左归饮连续给药对Cyp2b1、Cyp2c7和Cyp2c11酶活性的影响均无统计学意义(P>0.05)。结论左归饮配伍其他药物使用对代谢酶无明显影响,左归饮可在临床上广泛地配伍应用。Objective To investigate the effect of Zuogui Decoction on the metabolic activities of cytochrome P450 subtype enzymes Cyp2b1, Cyp2c11, and Cyp2c7 in rats using the “cocktail” probe drug method, and to provide an experimental basis for the development and application of Zuogui Decoction. Methods Amodiaquine, bupropion, and omeprazole were selected as the probe substrates for Cyp2b1, Cyp2c11, and Cyp2c7, respectively, and a cocktail solution was prepared. Male Sprague-Dawley rats were divided into experimental group and blank group. The rats in the experimental group were treated with high-, medium-, or low-dose Zuogui Decoction every morning by gavage, and those in the blank group were treated with the blank solvent every morning by gavage. Both groups were treated for 14 consecutive days. On the morning of day 14, the mixture of probe drugs was injected via the caudal vein, and the plasma concentration of the probe drugs was measured at several time points after injection.The DAS 2.0 software was used to calculate pharmacokinetic parameters of the probe drugs, and the effect of Zuogui Decoction on the activities of metabolic enzymes was evaluated. Liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the three probe drugs simultaneously. Results There were no significant differences in the activities of Cyp2b1, Cyp2c7, and Cyp2c11 after continuous administration of blank solvent or high-, medium-, or low-dose Zuogui Decoction between the blank group and the experimental group （ P 〉0.05）. Conclusion When used in combination with other drugs, Zuogui Decoction has no significant effect on the activities of metabolic enzymes. Therefore, it holds promise for clinical application.

关 键 词：左归饮 液质联用法 代谢酶 细胞色素氧化酶 

分 类 号：R285.5[医药卫生—中药学]