乌头汤对大鼠肝药酶CPY3A4活性的影响

Influence of Wutou Tang on Activity of CPY3A4 in Rat Liver Microsomes

摘要:

目的: 考察乌头汤对大鼠肝药酶CPY3A4活性的影响,以探索乌头汤作用于CPY3A4 发生药物间相互作用的可能性。 方法: 50只SD雄性大鼠随机分为空白对照组、抑制剂SKF-525A阳性组(0.1 g·kg^-1)、乌头汤高剂量组(原方剂量2倍)、乌头汤中剂量组(原方剂量)、乌头汤低剂量组(原方剂量1/2)。大鼠连续灌胃给药7 d,第8 d处理动物并制备肝微粒体,以睾酮为探针,采用超高效液相色谱(UPLC)测定6β-羟基睾酮的生成量,计算其代谢速率并评价CPY3A4活性的变化。 结果: 与空白对照组相比,乌头汤高、中、低剂量组的睾酮代谢速率均明显降低(P<0.05);与乌头汤低、中剂量组相比,乌头汤高剂量组的睾酮代谢速率皆降低。 结论: 乌头汤连续给药7 d后可抑制大鼠肝脏CPY3A4的活性,提示乌头汤与CPY3A4 底物药物合用时可能发生药物间相互作用。

Abstract:

Objective: The goal of the present study is to explore the interactions between Wutou Tang and CYP3A4 enzyme by determining the influence of Wutou tang on the activity of CPY3A4 in rat liver microsomes. Method: Fifty male SD rats were randomly divided into five groups. 3 groups were intragastrically treated with Wutou tang high dose (2 times of the original prescription dose), medium dose (original prescription dose) and low dose (0.5 times of the original prescription dose) for 7 consecutive days, respectively. Drinking water was given intragastrically to blank control group and SKF-525A (0.1 g·kg^-1) was given intragastrically to inhibitory control group. The activity of CPY3A4 was determined by UPLC method using testosterone as probe in vitro. Result: Compared with the blank control group, the testosterone metabolic rates were significantly lower of groups which were treated with Wutou tang high dose, medium dose and low dose (P<0.05). The testosterone metabolic rates of Wutou tang high dose group was lower than Wutou tang medium dose group and low dose group. Conclusion: The activity of CPY3A4 was significantly inhibited with the continuous use of Wutou tang, which indicates that taking Wutou tang with CYP3A4 enzyme substrates might cause drug interactions.