丹参注射液对大鼠肝微粒体CYP450亚型酶体外抑制作用

Inhibitory effect of Danshen Injection on rats liver cytochrome P450 enzyme in vitro

目的评价丹参注射液在体外对大鼠肝微粒体细胞色素P450(CYP450)亚型酶活性的影响。方法将丹参注射液分别与5种CYP450亚型酶(CYP1A2、CYP2C9、CYP2C19、CYP2D6、CYP3A4)的特异性探针底物非那西丁、甲苯磺丁脲、奥美拉唑、右美沙芬与大鼠肝微粒体进行孵育,采用UPLC-MS/MS法测定对应5种代谢产物对乙酰氨基酚、4-羟基甲苯磺丁脲、5-羟基奥美拉唑、右啡烷、N-去甲右啡烷的含有量并计算其IC50。结果丹参注射液对CYP1A2、CYP3A4的IC50值均大于100μg/m L,对CYP2C9、CYP2C19和CYP2D6的IC50值分别是3.32、16.44、0.30μg/m L。结论丹参注射液对CYP1A2、CYP3A4没有抑制作用,但对CYP2C19和CYP2C9分别有弱和中等抑制作用,对CYP2D6表现出强抑制作用。

AIM To investigate the inhibitory effect of Danshen Injection on the activities of five rat cytochrome P450 enzymes in vitro. METHODS Danshen Injection was incubated with five specific probes（phenacetin,orinase, omeprazole, dextromethorphan, and dextrorphan） belonging to five cytochrome P450 enzymes（CYP1A2,CYP2C9,CYP2C19,CYP2D6,CYP3A4） originated from rat liver microsome,respectively. Their five metabolites（including acetaminophen,4-hydroxy tolbutamide,5-hydroxy omeprazole,dextrorphan,N-demethyl dextrorphan） were analyzed by UPLC-MS/MS assay. The IC50 values were calculated. RESULTS Danshen Injection IC50 values of CYP1A2 and CYP3A4 were more than 100 μg/m L,and of CYP2C9,CYP2C19 and CYP2D6 were 3. 32 μg/m L,16. 44 μg/m L,and 0. 30 μg/m L,respectively. CONCLUSION The inhibitory effects of Danshen Injection on the activities of CYP2C9,CYP2C19,CYP2D6 are medium,weak and strong,respectively,but no effect on the activities of CYP1A2 and CYP3A4.