浙江不同产地浙贝配伍乌头对大鼠肝细胞色素P450重要同工酶含量的影响

Effects of Fritillaria Thunbergii from Zhejiang Different Habitat Coadministration with Aconitum on Liver CYP450 Isozymes in Rats

研究浙江不同产地浙贝配伍乌头对大鼠肝细胞色素P450重要同工酶活性的影响。方法:应用HPLC-UV测定CYP450三种同工酶的特异性探针底物咖啡因(CYP1A2)、氨苯砜(CYP3A4)和氯唑沙宗(CYP2E1)的代谢速率,评价各实验组对大鼠肝细胞色素P450重要同工酶的诱导或抑制作用。结果:①与乌头组比较,磐安浙贝及缙云浙贝配伍乌头后,都显著性诱导了CYP1A2,但鄞州浙贝配伍乌头后对CYP1A2活性的诱导作用不明显。浙江不同产地浙贝单用组对CYP1A2的影响两两间比较无统计学差异;浙江不同产地浙贝配伍乌头组两两间比较发现,鄞州浙贝配伍乌头组的CYP1A2活性显著性弱于其它两个产地浙贝配伍乌头组。②与乌头组比较,浙江不同产地浙贝配伍乌头组都明显抑制了CYP3A4,并且两两间比较无统计学差异。鄞州浙贝单用组CYP3A4的活性较缙云浙贝单用组弱,有统计学差异。③与乌头组比较,浙江不同产地浙贝配伍乌头组对CYP2E1都具有明显诱导作用,但是两两间比较无统计学差异。三种产地浙贝单用组对CYP2E1活性的影响两两间无统计学差异。结论:浙江不同产地的浙贝配伍乌头对CYP1A2和CYP2E1的活性有明显的诱导作用,而对于CYP3A4有明显的抑制作用。

Objective： To determine the inhibitory or inductive effects of Fritillaria thunbergii from Zhejiang different habitat coadministration with Aconitum on liver CYP450 isozymes in rats.Methods： The liver microsomes was prepared for the determination of the metabolic rates of three probe drugs to reflect the activity of liver microsamal CYP450 isozymes by HPLC-UV.Results： ①Compared with the Aconitum group,Fritillaria thunbergii from Pan＇an and Jinyun coadministration with Aconitum can induce the activity of CYP1A2 markedly,while Fritillaria thunbergii from Yinzhou coadministration with Aconitum has no obviously induction.The activity of CYP1A2 of the three groups which applied with Fritillaria thunbergii from Zhejiang different habitats only has no differences among them.But after they coadministration with Aconitum,Fritillaria thunbergii from Yinzhou has lower activity of CYP1A2 compared with the other two groups.②Compared with the Aconitum group,all groups applied with Fritillaria thunbergii from Zhejiang different habitats coadministration with Aconitum can obviously inhibit the activity of CYP3A4,and there is no difference among them.Yet,the activity of the group applied with Fritillaria thunbergii from Yinzhou is lower than that of Fritillaria thunbergii from Jinyun.③Compared with the Aconitum group,all groups applied with Fritillaria thunbergii from Zhejiang different habitats coadministration with Aconitum can obviously induce the activity of CYP2E1,and there is no difference among them.And the activity of CYP2E1 also has no differences among the groups applied with Fritillaria thunbergii from Zhejiang different habitats.Conclusion：All groups applied with Fritillaria thunbergii from Zhejiang different habitats coadministration with Aconitum can obviously induce the activity of CYP1A2 and CYP2E,yet,they can obviously inhibit the activity of CYP3A4.