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目的:研究抗癌药多西紫杉醇(DOC)对SD大鼠肝细胞CYP3A1代谢酶的影响。方法:将20只雄性SD大鼠随机分为空白对照组(尾静脉推注给予生理盐水,1mL/只,1次/d,连续3d)、地塞米松诱导组〔灌胃给予地塞米松,100mg/(kg·d),连续3d〕、DOC高剂量实验组〔尾静脉推注给予DOC,30mg/(kg·d),连续3d〕、DOC低剂量实验组〔尾静脉推注给予DOC,20mg/(kg·d),连续3d〕。采用HPLC法检测以睾酮为探针药物经大鼠肝微粒体温孵后转化的代谢产物6β-羟基睾酮的生成速率,以评价各组间CYP3A1酶的活性。结果:DOC高、低剂量组6β-羟基睾酮的生成速率,分别为(221.1±79.7)和(254.5±189.8)ρmol/mgproteinmin,空白对照组和地塞米松组分别为(249.1±81.4)和(1781.4±507.7)ρmol/mgpro-teinmin;经统计学检验表明,DOC高、低剂量组6β-羟基睾酮的生成速率与地塞米松诱导组的差异有统计学意义,P<0.01,与空白对照组的差异无统计学意义,P>0.05。结论:DOC对大鼠肝细胞CYP3A1酶活性无诱导作用。
Objective: To study the effect of docetaxel (anticancer drug) on CYP3A1 metabolic enzymes in hepatocytes of SD rats. Methods: Twenty male Sprague-Dawley rats were randomly divided into blank control group (normal saline, 1 mL / d, once daily for 3 d), dexamethasone group (dexamethasone, DOC (30mg / (kg · d) for 3 days) in high-dose DOC group (experimental group, 100mg / (kg · d) 20mg / (kg · d), continuous 3d〕. The production rate of 6β-hydroxytestosterone, a metabolite of testosterone, which is a probe drug, was incubated with rat liver microsomes after incubation by HPLC to evaluate the activity of CYP3A1 enzyme. RESULTS: The rates of 6β-hydroxytestosterone production in high and low dose DOC groups were (221.1 ± 79.7) and (254.5 ± 189.8) ρmol / mgproteinmin, respectively, and those in blank control group and dexamethasone group were (249.1 ± 81.4) and 1781.4 ± 507.7) ρmol / mgpro-teinmin. The statistical analysis showed that there was a significant difference between the high and low dose groups of 6β-hydroxytestosterone and the dexamethasone group (P <0.01) The difference was not statistically significant, P> 0.05. Conclusion: DOC has no effect on CYP3A1 activity in rat hepatocytes.