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本文研究蛇床子素(Osthol,Ost)在游离大鼠肝细胞中的代谢特征;探讨参与Ost体外代谢的CYP450亚酶及其对Ost代谢的影响。采用HPLC-UV检测法测定游离大鼠肝细胞温孵体系中Ost的含量;从温孵时间、肝细胞含量、底物浓度3个方面考察Ost的代谢特征;探讨CYP2C8抑制剂槲皮素(Que)、CYP2C9抑制剂磺胺嘧啶(Sul)、CYP2D6抑制剂育亨宾(Yoh)、CYP3A4抑制剂醋竹桃霉素(Tro)、CYP450诱导剂利福平(Rif)对Ost体外代谢的影响。结果表明,Ost在游离大鼠肝细胞中呈现酶促动力学代谢特征;Rif可显著增加Ost在肝细胞中的代谢;Yoh、Sul和Que对Ost的代谢无明显影响;Tro在0～200μmol·L-1内呈剂量依赖性地抑制Ost的代谢。CYP3A4介导了Ost的体外代谢,CYP2C8、CYP2C9和CYP2D6未参与Ost在大鼠肝细胞中的代谢。
This study was to investigate the metabolic characteristics of Osthol, Ost in free rat hepatocytes, and to investigate the role of CYP450 subunits involved in the in vitro metabolism of Ost and their effects on the metabolism of Ost. The content of Ost in the incubating system of free rat hepatocytes was determined by HPLC-UV detection; the metabolic characteristics of Ost were examined from the aspects of incubation time, hepatocyte content, and substrate concentration; and the CYP2C8 inhibitor quercetin (Que) was investigated. ), CYP2C9 inhibitor sulfadiazine (Sul), CYP2D6 inhibitor yohimbine (Yoh), CYP3A4 inhibitor tracyobomycin (Tro), CYP450 inducer rifampicin (Rif) on the metabolism of Ost in vitro. The results showed that Ost showed a characteristic of enzymatic kinetic metabolism in free rat hepatocytes; Rif significantly increased the metabolism of Ost in hepatocytes; Yoh, Sul and Que had no significant effect on the metabolism of Ost; Tro at 0-200 μmol. L-1 inhibited the metabolism of Ost in a dose-dependent manner. CYP3A4 mediates the in vitro metabolism of Ost and CYP2C8, CYP2C9 and CYP2D6 are not involved in the metabolism of Ost in rat hepatocytes.