紫草羟基萘醌对大鼠肝微粒体CYP2D6的影响

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。

Influence of Hydroxynaphthoquinone of Arnebia Euchroma (Royle) Johust. on Rat CYP2D6 Activity

OBJECTIVE To investigate the influence of hydroxynaphthoquinone of Arnebia Euchroma (Royle) Johust. (HNA) on CYP2D6 activity of Wistar rats. METHODS Liver microsomes of male Wistar rats were prepared after orally administrated HNA (5 and 60 mg·kg^-1·d^-1) or vehicle for 2 weeks. The CYP2D6 activity of rats was examined by the in vitro formation rate of dextrorphan metabolized from dextromethorphan. The effect of HNA on CYP2D6 was evaluated by comparing the data from administration groups with those from control group. RESULTS An accurate and rapid method was established to inspect CYP2D6 activity of rats by using dextromethorphan hydrobromide as a probe substrate. The study showed no significant differences on contents of microsome protein, cytochrome P450, cytochrome b5 and CYP2D6 activity among the administration groups and control group. CONCLUSION Oral administration of HNA for 2 weeks at dosage level ranging from 5 mg·kg^-1·d^-1 to 60 mg·kg^-1·d^-1 has no effect on CYP2D6 activity of Wistar rats. This result indicats that HNA orally administrated to rats has no significant inhibitory or inductive effect on CYP2D6 activity in liver microsome.