仙茅对正常/虚寒大鼠孕烷X受体及其介导的药物代谢酶CYP3A和运转蛋白P-gp的影响

Effect of rhizoma curculiginis on PXR,PXR-mediated CYP3A and P-gp in normal and deficiency cold rats

目的:明确仙茅对正常、虚寒大鼠孕烷X受体(PXR)调控药物代谢酶CYP3A和转运蛋白P-gp的作用差异,为探讨其药效表达差异机制奠定基础。方法:连续21d肌注氢化可的松粉针剂20mg·kg-1·d-1塑造虚寒大鼠模型。从第15天开始,正常、虚寒大鼠连续7d分别灌胃仙茅大、小剂量(30、20g/kg)水煎液。观察正常和虚寒状态下仙茅对PXR及其介导的药物代谢酶CYP3A和转运蛋白P-gp的影响。结果:仙茅大、小剂量分别给予虚寒大鼠后,能使虚寒大鼠降低的肝脏微粒体CYP3A活性、小肠P-gp及肝脏PXR蛋白表达水平不同程度升高(P<0.05,P<0.01)。而仙茅大、小剂量分别给予正常大鼠后,各指标变化均不明显。结论:仙茅对虚寒状态的治疗作用可能与其可升高虚寒大鼠PXR及其介导的CYP3A和P-gp有关。

Objective： To explore the mechanisms of rhizoma curculiginis potency expression by indicating dif erent effect of rhizoma curculiginis on PXR, PXR-mediated CYP3A and P-gp in normal and deficiency cold rats. Methods： The deficiency cold rats were given Hydrocortisone Injection（20mg·kg-1·d-1） by Intramuscular for 21 days. Since the 15th day, the normal and deficiency cold rats were respectively administered intragastrically with water decoction of rhizoma curculiginis（30g/kg and 20g/kg） for 7 days. To observe the effect of rhizoma curculiginis on PXR, PXR-mediated CYP3A and P-gp in normal and deficiency cold rats. Results： Since the deficiency cold rats were given large and low dosages of rhizoma curculiginis, CYP3A activity of hepatic, P-gp protein expression level of small intestine and PXR protein expression level of hepatic were increased, with statistically signii cances（P〈0.05, P〈0.01）. But there was no change of CYP3A, P-gp and PXR in normal rats which were given large and low dosages of rhizoma curculiginis. Conclusion： It showes that up-regulation of PXR, PXR-mediated CYP3A and P-gp of deficiency cold rats may be related to the therapeutic effect of rhizoma curculiginis on deficiency cold state.