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目的研究紫草羟基萘醌(HNA)对大鼠肝微粒体CYP2D6的影响。方法 Wistar大鼠,♂,口服给予不同剂量的HNA(5,60 mg.kg-1.d-1)或等量的空白溶媒,连续给药2周后制备肝微粒体。以体外探针药物右美沙芬的代谢物右啡烷的生成速率来反映CYP2D6的活性,通过比较给药组与空白溶媒组酶活性的差异来评价HNA对大鼠肝微粒体CYP2D6的影响。结果建立了一种以右美沙芬为探针底物评价大鼠肝微粒体CYP2D6活性的方法。口服给予HNA两周后,两个剂量组大鼠的肝微粒体蛋白含量、细胞色素P450总量、b5含量以及CYP2D6的活性与空白溶媒组相比差异均无统计学意义。结论 5 mg.kg-1.d-1和60 mg.kg-1.d-1剂量的紫草羟基萘醌口服2周对Wistar大鼠肝微粒体CYP2D6的活性均无显著影响,没有明显的诱导或抑制作用。
Objective To study the effect of comfrey hydroxy naphthoquinone (HNA) on the liver microsomal CYP2D6 in rats. Methods Wistar rats were orally administrated with different doses of HNA (5,60 mg.kg-1.d-1) or blank control medium, and liver microsomes were prepared after continuous administration for 2 weeks. The activity of CYP2D6 was detected by the generation rate of dextrorphan, a metabolite of dextromethorphan, in vitro. The effect of HNA on CYP2D6 in rat liver microsomes was evaluated by comparing the enzyme activity of the drug-treated group with that of blank vehicle. Results A method for dextromethorphan probe substrate evaluation of rat liver microsomal CYP2D6 activity was established. After two weeks of oral administration of HNA, there were no significant differences in liver microsomal protein content, total cytochrome P450 content, b5 content, and CYP2D6 activity between the two dose groups and the blank vehicle group. Conclusions Oxygen periadhenylquinone 5 mg.kg-1.d-1 and 60 mg.kg-1.d-1 have no significant effect on the activity of CYP2D6 in liver microsomes for 2 weeks. There is no significant difference Induction or inhibition.