Cocktail探针药物法评价傣药"雅解沙把" 对大鼠肝药酶P450亚型CYP1A2、CYP2C19、CYP2E1、CYP3A4 活性的影响

目的:采用cocktail探针药物法研究傣药"雅解沙把"对肝细胞色素P450亚型CYP1A2、CYP2C19、CYP2E1、CYP3A4的影响。方法:将SD大鼠随机分为空白对照组、苯巴比妥钠组(10.8 mg/kg)、"雅解沙把"低剂量组(0.27 g生药/kg)和"雅解沙把"高剂量组(2.43 g生药/kg),按上述剂量灌胃给药,空白对照组灌胃蒸馏水。连续灌胃7天后处死动物,取肝脏制备肝微粒体,以甲硝唑为内标,建立HPLC方法检测Cocktail探针药物奥美拉唑、氯唑沙宗、咖啡因、氨苯砜的代谢情况。结果:与空白对照组比较,"雅解沙把"低剂量组和高剂量组氯唑沙宗的代谢明显升高,氯唑沙宗的含量显著降低(P0.01),"雅解沙把"高剂量组奥美拉唑和氨苯砜的代谢明显升高,奥美拉唑和氨苯砜的含量明显降低(P0.05)。"雅解沙把"低剂量组和高剂量组虽咖啡因代谢较与空白对照组有上升的趋势,但差异无统计学意义(P0.05)。结论:傣药"雅解沙把"能促进肝药酶CYP3A4、CYP2C19、CYP2E1的活性,加速药物代谢,这可能是其解药物毒的作用机制之一。

Evaluation of the Effect of Dai Medicine "Yajieshaba" on the CytochromeP450 Isozymes CYP1A2, CYP2C19, CYP2E1, CYP3A4 by Cocktail ProbeDrugs

Objective:To study the effect of Dai medicine "Yajieshaba" on the cytochrome P450 isozymes CYP1A2, CYP2C19,CYP2E1, CYP3A4 by cocktail probe drugs.Methods:SD rats were randomized divided into the control group, phenobarbital group(10.8mg/kg), Yajieshaba low-dose group (0.27 g/kg), Yajieshaba high-dose group (2.43 g/kg). The grugs were given orally according to theabove doses. The control group was given distilled water. Cocktail probe drugs method was established to determine the four probes ofomeprazole, chlorzoxazone, caffeine, dapsone and the internal standard was metronidazole to evaluate the effect of CYP450 activity followingadministration of Yajieshaba.Results:Compared with the control group, the metabolism of chlorzoxazone in "Yajieshaba"low-dose group and high-dose group were significantly enhanced, the content of chlorzoxazone were decreased(P<0.01). the metabolismof omeprazole and dapsone in "Yajieshaba" high-dose group were significantly enhanced, and the content of omeprazole and dapsonewere decreased (P<0.05). "Yajieshaba" low-dose group and high-dose group have a trends to promote the metabolism of caffeine, butcompared with the control group, no statistical difference was founf (P>0.05).Conclusion:Dai medicine "Yajieshaba" could promote theactivity of hepatic cytochrome P450 isozymes CYP3A4, CYP2C19, CYP2E1 to accelerate the metabolism of drugs, which might be oneof the mechanisms on "Solutions of drug toxicity".