疏血通注射液对大鼠细胞色素P450酶6种亚型活性的影响

Effects of Shuxuetong Injection on Activities of Six Isoforms of Cytochrome P450 in Rats

目的用Cocktail探针药物法,研究疏血通注射液对大鼠细胞色素P450酶(CYP450)6种亚型活性的影响。方法将Wistar雄性大鼠随机分组,实验组给予疏血通注射液,空白组给予生理盐水,诱导7 d,分别以咖啡因、甲苯磺丁脲、奥美拉唑、美托洛尔、氯唑沙宗、氨苯砜作为CYP1A2、CYP2C9、CYP2C19、CYP2D6、CYP2E1、CYP3A1/2的探针药物。HPLC法检测探针药物的血药浓度,DAS软件估算药动学参数。结果与空白组相比,咖啡因和氨苯砜的t1/2、AUC0-t、AUC0-∞均显著增大,CL/F显著降低(P<0.05);氯唑沙宗的AUC0-t、AUC0-∞显著降低,CL/F显著增大(P<0.05);而甲苯磺丁脲、奥美拉唑、美托洛尔的药代动力学参数无显著性差异。结论疏血通注射液对大鼠CYP1A2、CYP3A1/2亚型的活性有抑制作用,能诱导CYP2E1亚型的活性,而对CYP2C9、CYP2C19和CYP2D6亚型的活性无显著影响。

Objective To investigate the effects of Shuxuetong injection （SI） on activities of six isoforms of cy- tochrome P450（CYP450） by Cocktail probe drugs in rats. Methods Male Wistar rats were randomly divided into SI group and blank control group, which were given SI or normal saline for 7 days. Caffeine, tolbutamide, omeprazole, metoprolol, chlorzoxazone and dapsone were used as probe drugs for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A1/2, respectively. HPLC method was used to determine the concentrations of probe drugs in rat plasma. And pharmacokinetic parameters were estimated by DAS. Results Compared with the blank control group, t1/2, AUC0-4 and AUC0-∞ of caffeine and dapsone were significantly increased, and CL/F was significantly decreased （P 〈 0.05）. Moreover, in SI group, AUC0-1and AUC0-∞ of chlorzoxazone were lower, and CL/F was higher than those in the blank control group（P 〈 0.05）. However, No significant difference of plasma concentrations and pharmacokinetics for tolbutamide, omeprazole and metoprolol was shown between SI group and the blank control group. Conclusion Shuxuetong injection can inhibit CYP1A2 and CYP3A 1/2 activities significantly, and induce CYP2E1 activity signif- icantly, but has no effect on the activities of CYP2C9, CYP2C19 and CYP2D6.