Cocktail法评价注射用益气复脉(冻干)对大鼠肝微粒体CYP1A2、CYP3A的诱导作用

摘要

Objective: To investigate the effect of Yi Qi Fu Mai Injection (YQFM) (Lyophilized) on the activity of cyto-chrome P450 (CYP1A2, CYP3A) in rats. Method: Healthy wistar rats raised ethically were pretreated with YOFM(Lo-phhilized) via the caudal vein once daily for consecutive seven days, and then hepatic microsomes were prepared. A cocktail selective substrates consisting of the phenacetin (PN,CYP1A2) and testosterone (TS,CYP3A) was incubated with rat livermicrosomes. Determined by HPLC method, the formation rates of acetaminophen and 6β-OH testosterone, the metabolites of the probe drugs were used as an indicator to estimate the activity of CYP1A2 and CYP3A. Result: The formation rates of acetaminophen were(18.04 ± 1.00) ,(43. 07 ±2.90) , (27. 6 ±4. 5) ng o ( mg protein)-1 min-1 ,The formation rates of 6β -OH testosterone were(15.79 ± 1.43 ) , (40. 86 ± 3. 32) , (32. 8 ± 3. 67 ) ng o ( mg protein) -1 o min-1. Conclusion; YQFM has an induced effect on the activity of CYP1A2 and CYP3A.%目的:研究注射用益气复脉(冻干)Yi Qi Fu Mai Injection( YQFM) (Lyophilized)对大鼠肝微粒体CYP1A2、CYP3A的诱导作用.方法:将wistar大鼠分为生理盐水对照组,苯巴比妥钠诱导组,YQFM组,连续给药7天后处死,制备肝微粒体.采用Cocktail法,将特异性探针底物非那西丁(CYP1A2)、睾酮(CYP3A)与肝微粒体共孵育,采用高效液相色谱测定孵育所得代谢产物对乙酰氨基酚和6β一羟基睾酮的生成速率,来评价YQFM对CYP1A2、CYP3A的诱导作用.结果:空白对照组、诱导组和YQFM组的对乙酰氨基酚的生成速率分别为(18.04±1.00)、(43.07±2.90)、(27.6±4.5) ng·(mg protein)-1·min-1,6β-羟基睾酮的生成速率分别为(15.79±1.43)、(40.86±3.32)、(32.8±3.67 )ng·(mg protein) -1·min -1.结论:YQFM对大鼠肝微粒体CYP1A2、CYP3A有诱导作用.