中国中药杂志

2011, v.36(19) 2710-2714

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天王补心丸中生地黄、玄参、天冬和麦冬水提液对大鼠肝CYP450酶含量及其亚型CYP3A,CYP2E1和CYP1A2活性的影响
Effect of water extract from traditional Chinese medicines Rehmannia glutinosa,Scrophularia ningpoensis,Asparagus cochinchinensis and Ophiopogon japonicas on contents of CYP450 and activities of CYP3A,CYP2E1 and CYP1A2 in rat

武佰玲;刘萍;高月;王宇光;
WU Bailing1,LIU Ping1*,GAO Yue2,WANG Yuguang2(1.Traditional Chinese Medicine Pharmacy of PLA General Hospital,Beijing 100853,China; 2.Institute of Radiation Medicine,Academy of Military Medical Science,Beijing 100850,China)

摘要(Abstract):

目的:研究天王补心丸中滋阴类药味生地黄、玄参、天冬和麦冬水提物对大鼠肝肝药酶(CYP450)含量及对亚型CYP3A,CYP2E1,CYP1A2活性的影响,探讨CYP450在天王补心丸代谢中的作用。方法:大鼠灌胃给予生地黄、玄参、天冬和麦冬水提物7 d后取肝脏称重并制备肝微粒体,紫外分光光度法测定肝微粒体细胞色素b5(Cytb5),P450的含量及CYP3A的活性,高效液相法测定CYP2E1和CYP1A2的活性。结果:与空白对照组比较,各给药组大鼠肝指数无显著变化;生地黄组CYP450含量极显著减少(P<0.01),CYP3A活性极显著增加(P<0.01),CYP1A2活性显著增加(P<0.05);玄参组CYP450含量减少(P<0.05),CYP3A和CYP1A2活性均极显著增加(P<0.01);天冬组Cytb5含量增加(P<0.05),CYP2E1活性增加(P<0.05),CYP1A2活性极显著增加(P<0.01);麦冬组Cytb5,CYP450含量无统计学差异,CYP3A活性增加(P<0.05),CYP2E1活性增加(P<0.05),CYP1A2活性极显著增加(P<0.01)。结论:天王补心丸中生地黄、玄参降低大鼠肝脏CYP450酶含量并均诱导CYP3A和CYP1A2活性,天冬诱导CYP2E1和CYP1A2活性,麦冬诱导CYP3A,CYP2E1和CYP1A2活性。由于抑制CYP450活性,减少对其他药代谢,滋阴药组在天王补心丸全方配伍中可增强其他各功能组比如补血养血、宁心安神类药味的作用,为探讨天王补心丸的配伍机制提供了理论基础。
Objective: To study the effects of the water extract of Rehmannia glutionsa,Scrophularia ningpoensis,Asparagus cochinchinensis and Ophiopogon japonicas,which are the drug from Tianwang Buxin Wan from nourishing vin,on the content of cytohrome P450(CYP450) in rat and the activities of CYP3A,CYP2E1 and CYP1A2 to investigate the role of CYP450 in the biotransformation of Tianwang Buxin Wan.Method: The rats were killed after administrated with extracts once daily for consecutive 7 days,the livers were removed rapidly and weighed,liver microsomes were prepared with ultra-centrifuge method,the contents of liver microsomal CYP450,cytochrome b5(Cytb5) and the activities of CYP3A were examined by ultraviolet spectrophotometry,the activities of CYP2E1 and CYP1A2 were determined by high performance liquid chromatography(HPLC).Result: All groups had no difference in the levels of liver indexe compared with normal sodium group.the water extract of R.glutionsa obviously decreased the contents of P450(P<0.01)and increased the activity of CYP3A(P<0.01) and CYP1A2(P<0.05).The water extract of S.ningpoensis decreased the contents of P450(P<0.05) and significantly increased CYP3A and CYP1A2 activities(P<0.01).A.cochinchinensis increased content of Cytb5(P<0.05) in rat and increased the activity of CYP2E1(P<0.05) and CYP1A2(P<0.01).O.japonicas had no significant difference on the contents of CYP450 and Cytb5 while increased the activities of CYP3A(P<0.05),CYP2E1(P<0.05) and CYP1A2(P<0.01).Conclusion: R.glutionsa and S.ningpoensis could decrease the content of CYP450 enzyme in rat liver and induct the activities of CYP3A and CYP1A2.A.cochinchinensis could induct the activities of CYP2E1 and CYP1A2.O.japonicus could induction the activities of CYP3A,CYP2E1 and CYP1A2 in Tianwang Buxin Wan.By inhibiting CYP450 activity to decrease the metabolism of other drugs,the effect of other functional groups in the compatibility of Tianwang Buxin Wan can be enhanced,and a theoretical basis on studying the compatible mechanism can be provided.

关键词(KeyWords): 生地黄;玄参;天冬;麦冬;细胞色素P450;CYP3A;CYP2E1;CYP1A2
Rehmannia glutionsa;Scrophularia ningpoensis;Asparagus cochinchinensis;Ophiopogon japonicus;CYP450;CYP3A;CYP2E1;CYP1A2

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 武佰玲;刘萍;高月;王宇光;
WU Bailing1,LIU Ping1*,GAO Yue2,WANG Yuguang2(1.Traditional Chinese Medicine Pharmacy of PLA General Hospital,Beijing 100853,China; 2.Institute of Radiation Medicine,Academy of Military Medical Science,Beijing 100850,China)

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