仙茅体内代谢过程与药物代谢酶CYP3A的相关性研究

目的:探讨仙茅体内代谢过程与药物代谢酶细胞色素P4503A(CYP3A)的相关性,为进一步研究机体CYP3A活性变化对仙茅性-效表达的影响奠定基础。方法:SD雄性大鼠随机分为2组,即正常组和利福平组。利福平组每天灌胃给予200mg/kg药物混悬液,正常组给予等体积蒸馏水,连续7d,第8天每组各取6只大鼠一次性灌胃仙茅水煎液(20g/kg)后,分别于20、50、90、180min时眼眶取血测仙茅入血成分苔黑酚葡萄糖苷血药浓度,其他大鼠断头处死,取肝、小肠、肾测定CYP3A活性。结果:利福平组大鼠肝微粒体CYP3A活性明显升高(P0.05),小肠、肾微粒体CYP3A活性有升高趋势;利福平组大鼠各时间点血药浓度均低于正常组,且在20、50、90时差异有统计学意义(P0.05,P0.01)。结论:利福平诱导后大鼠肝微粒体CYP3A活性升高,而苔黑酚葡萄糖苷血药浓度明显降低,说明仙茅体内代谢过程与药物代谢酶CYP3A相关。

Correlation study between metabolic processes of Rhizoma Curculigini and drug metabolizing enzyme CYP3A

Objective: To discuss whether the metabolic processes of Rhizoma Curculigini was related to the drug metabolizing enzyme CYP3A,for furher providing the basis for the research of the influence of CYP3A activity changes to property-effect expression of the Rhizoma Curculigini.Methods: Male SD rats were randomly divided into two groups,namely the normal group and the Rifampicin group.Drinking water was given ig to normal group rats,and Rifampicin(200mg·kg-1·d-1) suspension was given ig to the Rifampicin group rats for 7 consecutive days.On the eighth day,6 rats selected from each group were given Rhizoma Curculigini(20mg·kg-1·d-1) water extracts one time.Some blood was taken from rat orbital for detecting plasma concentration at the 20min,50min,90min and 180min.Other rats were sacrificed for measuring the CYP3A activities in liver,small intestinal and kidney microsomes.Results: The activity of liver microsomes CYP3A was increased in the Rifampicin group(P<0.05),there was no significantly changes of small intestinal and kidney microsomes CYP3A activities.Plasma concentration was decreased in the Rifampicin group at 20min,50min,90min(P< 0.05,P< 0.01).Conclusions: The activity of liver microsomes CYP3A was increased and orcinol glucosid plasma concentration was decreased in the Rifampicin group.This evidence indicated that the metabolic processes of Rhizoma Curculigini may be related with the drug metabolizing enzyme CYP3A.