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目的分别研究大黄素在雌性和雄性大鼠肝微粒体中酶促动力学及胡椒碱对其代谢的影响。方法将系列浓度的大黄素分别与雌性或雄性大鼠肝微粒体进行体外共孵育,采用HPLC法测定孵育液中大黄素的浓度,并计算酶动力学参数。另将不同浓度的胡椒碱与大黄素在大鼠肝微粒体中进行共孵育,计算胡椒碱对大黄素代谢的抑制常数(Ki),进一步探讨其代谢抑制类型,并推测其对大黄素体内代谢的影响。结果大黄素在雌性和雄性大鼠肝微粒体中代谢的最大反应速率(Vmax)分别为(84.49±9.62)和(32.97±7.37)μmol·min~(-1)·mg protein~(-1),米氏常数(Km)分别为(60.50±8.71)和(34.48±4.96)μmol·L~(-1),内在清除速率(CLint)分别为(1 406±112)和(965±73.7)μL·min~(-1)·mg protein~(-1),雌性和雄性大鼠的Ki值分别为0.35和0.31μmol·L~(-1)。结论大鼠肝微粒体中胡椒碱抑制大黄素的葡萄糖醛酸代谢呈浓度依赖性,根据图形推断其抑制类型为混合性抑制,并推测合用胡椒碱后,大黄素在大鼠体内的血药浓度显著增加,为其进一步开发研究提供了参考依据。
Objective To study the enzymatic dynamics of emodin in liver microsomes of female and male rats and the effects of piperine on its metabolism. Methods Emodin was serially incubated with female or male rat liver microsomes in vitro. The concentration of emodin in the incubation solution was determined by HPLC and the enzyme kinetic parameters were calculated. In addition, different concentrations of piperine were incubated with emodin in rat liver microsomes to calculate the inhibitory constant (Ki) of piperine on the metabolism of emodin, to further explore the type of metabolic inhibition, and to speculate that emodin in vivo metabolism Impact. Results The maximal metabolic rate of emodin in liver microsomes of female and male rats were (84.49 ± 9.62) and (32.97 ± 7.37) μmol · min -1 · mg protein -1, respectively , And the Km were (60.50 ± 8.71) and (34.48 ± 4.96) μmol·L -1, respectively, and the CLint values were (1 406 ± 112) and (965 ± 73.7) μL, respectively · Min ~ (-1) · mg protein ~ (-1), Ki values of female and male rats were 0.35 and 0.31μmol·L -1, respectively. Conclusion Piperine inhibits the glucuronide metabolism of emodin in a concentration-dependent manner in rat liver microsomes. Based on the graph, it is concluded that the inhibitory mode is mixed inhibition, and speculated that piperine combined with plasma concentrations of emodin in rats A significant increase for the further development of research provides a reference.