丹红注射液对大鼠肝微粒体5种CYP亚型酶活性的影响

摘要

Objective To investigate the effects of danhong injection on the activities of five cytochrome P450 enzymes in vitro for clinical combination therapy. Methods Phenacetin, tolbutamide, dextrorphan, chlorozoxazone, testosterone were incubated as probes with or without danhong injection at low,middle and high concentrations. HPLC method was used to detect the substrate metabolites to study the effects of danhong injection on the activities of five cytochromes P450 enzymes. Results In vitro,the activities of CYP1A2 and CYP2C9 in danhong injection groups were lower than that in the blank group ( P<0. 05 ) ; but no significant difference was presented for CYP2D6 ,CYP2E1 and CYP3A4 in danhong injection groups compared with the control group ( P>0. 05 ). With the IC50 value and Kt value were 0. 54% and 0. 226% .respectively. Conclusion Danhong injection remarkably inhibits the activity of CYP1A2 in vitro in a mixed-type inhibition model. It also weakly suppresses the activity of CYP2C9,but not on CYP2D6,CYP2E1 ,CYP3A4 activities.%目的 研究丹红注射液对5种细胞色素P450亚型酶活性的影响,为临床合理用药提供参考.方法 采用大鼠体外肝微粒体孵育法,分别以非那西丁、甲苯磺丁脲、右美沙芬、氯唑沙宗、睾酮为CYP1A2、CYP2C9、CYP2D6、CYP2E1、CYP3A4的探针药物,在大鼠肝微粒体孵育体系中孵育,用高效液相色谱(HPLC)法测定相应的代谢产物,比较空白对照组和丹红注射液低、中、高剂量组之间探针药物代谢率的差异,评价丹红注射液对各亚型酶活性的影响.结果 在体外肝微粒体孵育体系中,丹红注射液低剂量组中CYP1A2 和CYP2C9活性与空白对照组相比,差异无统计学意义(P＞0.05);中和高剂量组中CYP1A2和CYP2C9活性与空白对照组相比降低,差异有统计学意义(P＜0.05或P＜0.01);丹红注射液低、中、高剂量组中CYP2D6、CYP2E1、CYP3A4的活性与空白对照组相比,差异无统计学意义(P＞0.05).丹红注射液对大鼠肝微粒体CYP1A2酶活性的半数抑制浓度(IC50)和抑制常数(Ki)分别为0.54%和0.226%.结论 丹红注射液对大鼠肝微粒体CYP1A2酶活性有抑制作用,且为混合型抑制;对CYP2C9有弱抑制作用;对CYP2D6、CYP2E1、CYP3A4酶活性无明显影响.