石斛碱和石斛酚对小鼠细胞色素P450表达与活性作用研究

Effects of Dendrobine and Gigantol on Hepatic Cytochrome P450 Expression and Activity in Mice

目的:探究石斛碱和石斛酚对小鼠肝脏主要细胞色素P450表达和活性的影响。方法:将C57BL/6小鼠随机分为对照组、石斛碱(0.5、1.5、3 mg·kg^(-1))组和石斛酚(0.02、0.05、0.1 mg·kg^(-1))组,经腹腔注射给药2周。采用差速离心法提取小鼠肝微粒体,Western blot分析主要P450酶亚型的表达。底物探针法测定P450酶活性。结果:West‑ern blot结果显示,石斛碱显著诱导小鼠肝脏CYP1A1、CYP1A2、CYP2B10和CYP2C19蛋白的表达,而石斛酚显著诱导小鼠肝脏CYP1A1、CYP1A2、CYP3As、CYP2B10、CYP2C19和CYP2E1蛋白的表达,而酶活性结果显示只有CYP1A1酶活性被石斛碱显著诱导。结论:石斛碱可能通过诱导CYP1A1酶来加速药物代谢,提示与石斛碱合用时需注意CYP1A1酶代谢的药物的用量。

Objective:The aim of this study was to investigate the effects of dendrobine and gigantol on the expression and activities of cytochromes P450 in the mouse liver.Methods:Male C57BL/6 mice were randomly divided into seven groups,including a control group,dendrobine(0.5,1.5,and 3 mg·kg^(-1))groups,and gigantol(0.02,0.05,and 0.1 mg·kg^(-1))groups,and treated for 2 weeks by intraperitoneal injection.Mouse liver microsomes were extracted by differential centrifugation,and western blot analysis was used to determine the expression of major CYP isoforms.Furthermore,CYP enzyme activity was mea‑sured using a substrate probe method.Results:The western blot results showed that the expression levels of CYP1A1,CYP1A2,CYP2B10 and CYP2C19 in the mouse liver were moderately induced by den‑drobine,while that of CYP1A1,CYP1A2,CYP3As,CYP2B10,CYP2C19,and CYP2E1 were moder‑ately induced by gigantol.However,only CYP1A1 activity was increased by dendrobine.Conclusion:den‑drobine might accelerate the drug metabolism through activating CYP1A1 enzyme,and it is necessary to pay attention to the dosage of the drugs which are metabolised by CYP1A1 enzyme when they are com‑bined with dendrobine in therapy.