水黄皮素在大鼠肝微粒体中的代谢研究  

Study on the metabolism of karanjin in the rat liver microsome

作　　者：王春艳[1,2] 汤明海[2] 李容[1] 李小彬[1,2] 王海蓉[1,2] 万丽[1] 

机构地区：[1]成都中医药大学药学院,四川成都611137 [2]四川大学生物治疗国家重点实验室,四川成都610041

出　　处：《华西药学杂志》2015年第3期333-335,共3页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:81374017)

摘　　要：目的研究水黄皮素在大鼠肝微粒体中的代谢稳定性,确定水黄皮素的代谢酶表型。方法将水黄皮素与大鼠肝微粒体于37℃孵育,应用UPLC-MS/MS法检测孵育液中水黄皮素的含量,考察水黄皮素的代谢稳定性。将水黄皮素与各细胞色素P450(CYP)酶中的各同工酶CYP2E1、2C19、1A2、2D6、2C9和3A4的特异性抑制剂共孵育,确定其代谢酶表型。结果在大鼠肝微粒体中,水黄皮素的t1/2=1.97 h、Cl=0.70 m L·h-1·mg-1,CYP1A2是其主要代谢酶。结论水黄皮素在大鼠肝微粒体中是由多个CYP同工酶介导代谢的,其中,CYP1A2酶的介导作用最强。OBJECTIVE To investigate the metabolic stability of karanjin in the rat liver microsomes in vitro,and to identify the metabolic phenotyping. METHODS Karanjin was incubated at 37 ℃ with rat liver microsome. The concentrations of karanjin in the incubation systems were determined by a UPLC-MS / MS method to evaluate the metabolic stability of karanjin. The cytochrome P450（ CYP） phenotyping of karanjin was identified using specific inhibitors of CYP isoforms（ CYP2E1,2C19,1A2,2D6,2C9 and 3A4） in the rat microsomal incubation system. RESULTS In rat liver microsome,karanjin could be metabolically eliminated in the presence of NADPH. The t1 /2of karanjin was 1. 97 hour. The extrapolated hepatic clearance was 0. 70 m L·h^-1·mg^-1. The results of CYP phenotyping indicated that CYP1A2 was mainly involved in the metabolism of karanjin. CONCLUSION Karanjin was mainly metabolized by a number of CYP isoenzymes in rat liver microsome,CYP1A2 was the major metabolic enzymes responsible for the metabolism of karanjin.

关 键 词：水黄皮素 大鼠肝微粒体 代谢 稳定性 代谢酶表型 超高效液相色谱-串联质谱 细胞色素P450酶 清除率 

分 类 号：R917[医药卫生—药物分析学]