目的研究延胡索总生物碱(TA)中延胡索乙素(TET)在肝微粒体中的酶促反应动力学,并比较白芷有效组分白芷香豆素(Cou)、挥发油(VO)与TA配伍后对TET酶促反应动力学的影响。方法超速离心法制备大鼠肝微粒体,采用高效液相色谱法测定孵育液中TET原形药物的浓度。比较TA、TA-Cou、TA-VO、TA-Cou-VO配伍各组中TET的酶促反应动力学,推导出药物米氏常数(K_m)和最大反应速度(V_max);并计算TET肝内清除率(CL_int)。结果 TA配伍组中的TET在大鼠肝微粒体内代谢反应的Vmax、Km和CLint分别为0.12μmol/(L.min.mg)、5.40μmol/L、0.022 L/(min.mg);TA-Cou组分别为0.27μmol/(L.min.mg)、40.18μmol/L、0.006 L/(min.mg);TA-VO组分别为0.57μmol/(L.min.mg)、22.60μmol/L、0.025 L/(min.mg);TA-Cou-VO组分别为0.84μmol/(L.min.mg)、23.25μmol/L、0.036 L/(min.mg)。结论 TA配伍白芷有效组分可降低TA中TET在肝内的CL_int。

Objective To study the enzymatic reaction kinetics of dl-tetrahydropalmatine(TET) in total alkaloid(TA) of Corydali Rhizoma in rat liver microsomes and to investigate the compatible effects of the effective components such as coumarin(Cou) and volatile oil(VO) in Angelicae Dahuricae Radix with TA in Corydali Rhizoma on enzymatic reaction kinetics of TET.Methods Rat liver microsomes were prepared by ultracentrifugation and the TET concentration in incubation medium was determined by HPLC.Comparative study on the enzymatic reaction kinetics of TET in each group of TA,TA-Cou,TA-VO,and TA-Cou-VO to deduce the michaelis constant(Km) and maximum reaction rate(Vmax) of TET in each group and calculate the clearance rate(CLint) of TET in each group.Results The Km,Vmax,and CLint in TA group were 0.12 μmol/(L.min.mg),5.40 μmol/L,and 0.022 L/(min.mg),respectively;In TA-Cou group they were 0.27 μmol/(L.min.mg),40.18 μmol/L,and 0.006 L/(min.mg),respectively;In TA-VO group they were 0.57 μmol/(L.min.mg),22.60 μmol/L,and 0.025 L/(min.mg),respectively;In TA-Cou-VO they were 0.84 μmol/(L.min.mg),23.25 μmol/L,and 0.036 L/(min.mg),respectively.Conclusion The effective components of TA in Corydali Rhizoma with Cou and VO in Angelicae Dahuricae Radix could decrease CLint of TET in TA of liver.

国家自然科学基金资助项目(30960516);国家重大新药创制中药新型给药系统技术平台(2009ZX09310-005);江西省自然科学基金资助项目(2007GZY0932)