【摘要】 目的 研究黄芩苷葡醛酸化代谢稳定性及酶动力学特征，探究糖尿病状态对黄芩苷代谢的影响。方法 大鼠肝微粒体（RLMs）采用差速离心法制备；将黄芩苷分别与正常或糖尿病模型RLMs共孵育后，采用高效液相色谱法测定代谢产物的浓度，以“相关系数”对浓度进行校正；并计算酶动力学参数。结果 黄芩苷与RLMs共孵育后，可生成葡醛酸化代谢产物；其在3～300μmol·L^-1浓度范围内酶动力学符合米氏方程，在正常和糖尿病状态下的米氏常数（K_m）分别为（44.4±13.0）、（46.4±1.8）μmol·L^-1，最大反应速率(V_max)分别为（761.7±109.6）、（1 571.0±178.0） pmol·min^-1·mg^-1，内在代谢清除率(Cl_int)分别为18.5、33.7μL·min^-1·mg^-1；与对照组大鼠相比，黄芩苷在糖尿病RLMs中葡醛酸化代谢能力显著增强（P<0.05）。结论 黄芩苷在RLMs中可生成葡醛酸化代谢产物，糖尿病状态下可加快黄芩苷的代谢。更多还原

【Abstract】 Objective To study the stability and enzyme kinetics of glucuronidation metabolism of baicalin, and explore the effects of diabetes on baicalin metabolism. Methods Rat liver microsomes（RLMs） were prepared by the differential centrifugation method. Baicalin was metabolized in vitro by being incubated with normal and diabetic RLMs. The concentration of metabolites was determined by high performance liquid chromatography method and corrected by the "correlation coefficient", and the enzymatic kinetic parameters were calculated. Results After incubation with RLMs, baicalin could generate a glucuronide metabolite. The enzymatic kinetics within the concentration range of 3-300 μmol·L^-1 conformed to the MichaelisMenten equation. Under normal and diabetes conditions, the Michaelis constants（K_m） were（44.4±13.0） and（46.4±1.8） μmol·L^-1, respectively, and the maximum reaction rates(V_max) were（761.7±109.6） and（1 571.0±178.0） pmol·min^-1·mg^-1, respectively. The intrinsic metabolic clearance rates(Cl_int) were 18.5 and 33.7 μL·min^-1·mg^-1, respectively. Compared with normal rats, the glucuronidation metabolic capacity of baicalin in the diabetic rat liver microsomes was significantly enhanced（P<0.05）. Conclusion Baicalin can be metabolized into a glucuronide metabolite in rat liver microsomes, and the diabetic state can accelerate the glucuronidation metabolism of baicalin.更多还原