中文摘要：

目的研究大鼠肝微粒体温孵系统中盐酸小檗碱代谢动力学以及吴茱萸中多种化学成分对其代谢的影响。方法采用体外肝微粒体温孵法研究盐酸小檗碱代谢的酶动力学,分别考察了温孵时间、微粒体质量浓度以及底物浓度对盐酸小檗碱代谢速率的影响,并探讨吴茱萸中吴茱萸碱、吴茱萸次碱和吴茱萸内酯对其代谢的影响。结果盐酸小檗碱在大鼠肝微粒体温孵系统中发生较强的代谢,其在大鼠肝微粒体中37℃温孵0～60 m in呈时间依赖的线性消除;当肝微粒体蛋白浓度在0.5～2.0 mg.mL-1,温孵时间为60 m in时,盐酸小檗碱代谢速率表现出微粒体蛋白浓度依赖性增快;当底物盐酸小檗碱浓度大于10.0μg.mL-1时,盐酸小檗碱的代谢速率不再随底物浓度的增加而增加,表现出明显的饱和特性。其表观酶促动力学参数,米氏常数Km为（2.41±0.617）mg.mL-1,最大反应速度Vm ax为（6.88±1.89）μg.g-1.m in-1。吴茱萸碱、吴茱萸次碱和吴茱萸内酯均能显著抑制盐酸小檗碱的代谢,3个组分对盐酸小檗碱的代谢抑制常数Ki分别为（140.85±16.48）,（15.34±3.04）和（25.98±6.47）μmol.L-1,其中吴茱萸次碱和吴茱萸内酯的代谢抑制作用明显强于吴茱萸碱（P〈0.001）。结论盐酸小檗碱在大鼠肝微粒体内被迅速代谢;吴茱萸中化学成分吴茱萸碱、吴茱萸次碱和吴茱萸内酯对盐酸小檗碱的代谢有抑制作用,此结果有可能对小檗碱体内药动学产生影响。

英文摘要：

OBJECTIVE To investigate the metabolic kinetics of berberine in rat liver microsome and the effects of some chemical compositions in Wuzhuyu on berberine metabolism.METHODS By developing an in vitro system of rat liver microsomes,the factors including incubation time,microsomal protein concentration and original concentration of berberine were surveyed and the effect on berberine metabolism rate from diverse concentration of evodiamine,rutaecarpine and evodin was investigated.RESULTS Berberine was metabolized in rat liver microsomes.Berberine metabolism showed time（0-60 min） and microsomes protein concentration（0.5-2.0 mg·mL-1） dependented characteristics.The Michaelis-Menten parameters of Km and Vmax in rat microsomes were initially estimated by analyzing Lineweave-Brurk plot.The Km and Vmax of berberine were（2.41±0.617） mg·mL-1 and（6.88 ±1.89） ng·mg-1·min-1.All those three components from Wuzhuyu significantly inhibited the metabolism of berberine,moreover the inhibition effect of rutaecarpine and evodin were higher than that of evodiamine（P0.001）.CONCLUSION Berberine was rapidly metabolized in rat liver microsomes.Chemical compositions in Wuzhuyu can significantly inhibit the metabolism of berberine.This might be one significant mechanism of Huanglian and Wuzhuyu compatibility.