灯盏花素注射液对大鼠体外肝微粒体细胞色素P450酶活性的影响

摘 要 目的:研究灯盏花素注射液对大鼠肝微粒体CYP1A2、CYP2C9、CYP2D6、CYP2E1和CYP3A1/2 五个亚型酶活性的影响。方法: 采用大鼠肝微粒体体外孵育法，选用非那西丁（CYP1A2）、甲苯磺丁脲（CYP2C9）、右美沙芬（CYP2D6）、氯唑沙宗（CYP2E1）和睾酮（CYP3A1/2）作为5个亚型酶的探针药物，孵育系统中加入不同浓度的灯盏花素注射液，用HPLC法测定5个亚型酶探针药物代谢产物的生成量，比较空白对照组与不同浓度灯盏花素注射液给药组探针药物的活性，反映灯盏花素注射液对5个亚型酶活性的影响。结果:大鼠肝微粒体体外孵育系统中，灯盏花素注射液对大鼠CYP3A1/2的IC₅₀为29.40μg·ml^-1，K_i为37.78 μg·ml^-1；对CYP1A2、CYP2C9、CYP2D6和CYP2E1的IC₅₀＞200 μg·ml^-1。结论:灯盏花素注射液对大鼠体外肝微粒体CYP3A1/2有弱的抑制作用，对CYP1A2、CYP2C9、CYP2D6和CYP2E1活性无明显影响。

Effects of Breviscapines Injections on CYP Activities in Rat Liver Microsomes in vitro

Objective：To study the effects of breviscapine injections on the activities of CYP1A2,CYP2C9,CYP2D6,CYP2E1 and CYP3A1/2 enzymes in rat liver microsomes in vitro.Method：Phenacetin（CYP1A2）,tolbutamide（CYP2C9）,dextromethorphan （CYP2D6）,chlorzoxazone（CYP2E1） and testosterone（CYP3 A1/2） were selected as the five probe drugs of the enzymes in the microsomal incubation system.An HPLC method was used to determine the metabolites of the probe drugs in the blank control group and breviscapine injections groups with different concentrations of breviscapine to investigate the effects of the injections on the activities of CYP1A2,CYP2C9,CYP2D6,CYP2E1 and CYP3A1/2.Result：The IC_（50） of breviscapine injection on rat CYP3A1/2 enzyme was 29.40μg·ml~（-1） and the K_i was 37.78μg·ml~（-1）.The IC_（50） of CYP1A2,CYP2C9,CYP2D6 and CYP2E1 were more than 200μg ？ ml~（-1） in rat liver microsomal incubation systems.Conclusion：Mild inhibition effect of breviscapine injections on rat CYP3A1/2 enzyme in rat liver microsomal.incubation system in vitro is observed without effects on CYP1A2,CYP2C9,CYP2D6 and CYP2E1.