吴茱萸水煎液对大、小鼠肝药酶亚型影响的比较研究

A comparative study of effect of Euodiae Fructus decoction on activity of drug-metabolism enzymes in rat and mouse live microsome

目的比较吴茱萸水煎液对大鼠、小鼠肝药酶亚型的影响。方法取KM小鼠随机分为吴茱萸高剂量组(56 mg生药·g-1)、低剂量组(28 mg生药·g-1)和正常组,另取Wistar大鼠随机分为吴茱萸高剂量组(40 mg生药·g-1)、低剂量组(20 mg生药·g-1)和正常组,连续灌胃给予吴茱萸水煎液或等容量蒸馏水21 d后,采用药物探针法测定动物肝药酶亚型CYP1A、CYP2C、CYP2D、CYP2E1、CYP3A的活性。结果①小鼠实验结果显示,与正常组比较,吴茱萸高、低剂量组均诱导肝药酶亚型CYP1A、CYP2E1和CYP3A的活性(P<0.01),低剂量组诱导CYP2C活性(P<0.05);吴茱萸高、低剂量组对CYP2D活性无明显影响。②大鼠实验结果显示,与正常组比较,吴茱萸高、低剂量组均诱导肝药酶亚型CYP1A活性(P<0.01)。高剂量组诱导CYP2C和CYP2E1活性(P<0.05或0.01);吴茱萸高、低剂量组对CYP3A活性无明显影响;吴茱萸高、低剂量组均抑制CYP2D活性(P<0.01)。③实验结果对比显示,吴茱萸水煎液对大、小鼠肝药酶亚型的影响相同点是诱导了CYP1A、CYP2C及CYP2E1活性,尤其对CYP1A活性诱导更为明显。不同点是吴茱萸诱导了小鼠CYP3A活性,而对大鼠CYP3A活性无明显影响;吴茱萸对小鼠CYP2D活性无明显影响,而对大鼠CYP2D活性有明显抑制作用。结论吴茱萸水煎液对大、小鼠部分肝药酶亚型活性的影响有一定的差异性。

Aim To compare the effect of the activity of drug-metabolism enzymes caused by Euodiae Fructus decoction in rat and mouse liver microsome. Methods KM mice and Wistar rats were respectively divided into three groups ： normal control, high （56 mg . g-1 or 40 mg. g-l）,and low dose（28 mg . g-1 or 20 mg .g-1） treated groups, which were administered respec-tively with distilled water or equal volume of Euodiae Fructus decoction by gavage for consecutive 21 days. The activities of CYP1A, CYP2C, CYP2D, CYP2E1 and CYP3A in liver microsome were detected by using probe drug. Results @ In mice, compared with those in the control group, the activities of CYP1A, CYP2E1 and CYP3A were significantly induced in high and low dose groups （P 〈 0.01 ）, the activity of CYP2C was significantly induced in low dose group （P 〈 0. 05 ）, while the activity of CYP2D was not affected in high and low dose groups. @ In rats, compared with that in the control group, the activity of CYP1A was significantly induced in high and low dose groups （ P 〈 0. 01 ）, the activities of CYP2C and CYP2E1were significantly induced in high dose group （P 〈 0.05 or O. O1 ）, the activity of CYP3A was not affected in high and low dose groups, while the activity of CYP2D was significantly inhibited in high and low dose groups. （~） According to the results of the experiment in rats and mice, the similarity of the effect of Euodiae Fruc- tus on the activity of drug-metabolism enzymes in rat and mouse liver microsome was that the activities of CYP1A,CYP2E1 and CYP2C were all significantly in- duced in high and low dose groups, which was espe- cially obvious for CYP1A. The first difference was that the activity of CYP3A was significantly induced in mice, while that was not affected in rats. The second difference was that the activity of CYP2D was not af-fected in mice, while that was significantly inhibited in rats. Conclusion The activity of drug-metabolism en- zymes induced by Euodiae Fructus is different between rats and mice.