川楝子对大鼠肝细胞色素P450诱导作用的研究

Studies on the induction of cytochrome P450 in rats' liver induced by fructus toosendan

目的:考察川楝子对大鼠肝细胞色素P450 1A2、2E1、3A1活性的影响。方法:大鼠分组,连续灌胃给予150g生药/kg的川楝子7天;苯巴比妥组腹腔注射0.08g/kg的苯巴比妥3次。高效液相色谱法对肝细胞色素P450 1A2、2E1、3A1代谢能力进行测定。结果:连续给予川楝子7天后,对肝细胞色素P450 1A2代谢能力影响不明显,但可使大鼠肝微粒体酶蛋白含量增加,使肝细胞色素P450 1A2总代谢能力增强;对大鼠大鼠肝细胞色素P450 2E1活性及代谢能力均无明显影响;川楝子可诱导雌性大鼠大鼠肝细胞色素P450 3A1,使6-OH睾酮代谢生成速率及肝脏总代谢睾酮的能力增强;对雄性大鼠肝细胞色素P450 3A1有诱导的趋势,使6-OH睾酮代谢生成速率及肝脏总代谢睾酮的能力有增强的趋势,但与对照组比较差异无显著意义。结论:川楝子对大鼠肝细胞色素P450 3A1活性具有诱导作用。

Objective：To explore the effect of Fructus Toosendan（川楝子） on the activity of hepatic cytochrome P450 1A2、2E1 and 3A1 in rats.Methods： SD rats were divided into 3 groups： control group,Fructus Toosendan group and Phenobarbital group,respectively,then treated ig with distilled water,Fructus Toosendan 150g/kg and Phenobarbital 0.08g/kg,respectively.Then the metabolism capability of CYP 1A2、2E1 and 3A1 in hepatic tissue were detected by HPLC.Results： The effect on the activities of CYP1A2 had no significance after Fructus Toosendan was given by repeated administration for 7 days,but the proteinic contents of hepatic microsomal enzyme were increased（P〈0.05）,moreover,Fructus Toosendan could enhance the hepatic metabolic capabilities of CYP1A2（P〈0.05）;The effects on the activities and hepatic metabolic capabilities of CYP2E1 had no significance;Fructus Toosendan could induce the female rats’ hepatic microsomal enzyme CYP3A1,and could enhance the metabolism-production rate of 6-OH-testosterone（P〈0.05）,but the induction of male rats were not significantly compared to the normal rats,there were tendency only.Conclution： Fructus Toosendan could induce the activity of CYP450 3A1.