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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(Km)和最大反应速度(Vmax);并计算TET肝内清除率(CLint)。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CLint。
Objective To study the enzymatic reaction kinetics of tetrahydropalmatine (TET) in liver microsomes of total alkaloid (TA) of Rhizoma Corydalis and to compare the effects of the active ingredient of Angelica dahurica (Cou), volatile oil (VO) and TA Effect on TET Enzymatic Reaction Kinetics. Methods Rat liver microsomes were prepared by ultracentrifugation and the concentrations of TET-like drugs in the incubation solution were determined by high performance liquid chromatography. The kinetics of enzymatic reaction of TET in TA, TA-Cou, TA-VO and TA-Cou-VO compatibility groups were compared to get the Km and Vmax. Clearance rate (CLint). Results The Vmax, Km and CLint of TET in rat liver microsomes were 0.12μmol / (L.min.mg), 5.40μmol / L and 0.022 L / (min.mg), respectively. TA- Coucine group were 0.27μmol / (L.min.mg), 40.18μmol / L and 0.006 L / (min.mg) respectively, while TA-VO group was 0.57μmol / L.min.mg and 22.60μmol / L , 0.025 L / (min.mg); TA-Cou-VO group was 0.84μmol / (L.min.mg), 23.25μmol / L and 0.036 L / (min.mg) respectively. Conclusions TA combined with the effective components of Angelica dahurica can reduce the CLint of TET in the liver in TA.