药物代谢酶维生素E琥珀酸酯抑制苯并(a)芘

Relationship between pharmaceutical metabolism enzyme and inhibitory effect of VES on B(a)P

目的 探讨药物代谢酶在维生素E琥珀酸酯 (VES)抑制苯并 (a)芘毒性中的作用。方法 建立B(a)P诱导的小鼠前胃癌模型 ,观察不同途径投予VES对前胃癌的抑制作用。再选择最佳途径观察两相药物代谢酶在此过程中的变化。采用免疫荧光光度法检测小鼠肝脏微粒体 (S - 9组分 )中Ⅰ相药物代谢酶乙氧基异吩恶唑 0 -脱乙基酶(Ethoxyresorufin 0 -deethylase,EROD)活性 ;应用试剂盒测定S - 9组分中Ⅱ相药物代谢酶谷胱甘肽 -S -转移酶(GST)活性。结果 经口投予和腹腔注射VES均可明显降低B(a)P诱导的小鼠前胃癌的发生。VES可显著降低肝脏Ⅰ相药物代谢酶乙氧基异吩恶唑 0 -脱乙基酶 (EROD)的活性 (39 1± 3 0 5 ) ,与阳性对照组 (5 7 9± 3 16 )比较 ,有显著性差异。结论 VES可降低B(a)P诱导的小鼠前胃癌 ,作用机制可能是通过影响肝脏药物代谢酶的活性来实现。

Objective To study the role of the pharmaceutical metabolism enzyme during the inhibitory effect of VES against B(a)P in mice.Methods The model of B(a)P-induced forestomach cancer in mice would be established firstly to check whether there was any difference between the two kinds of demonstrating ways.Then to select the best way to do the following experiment.The activities of EROD and GST in liver S-9 fraction were measured by spectrophotofluorometer and GST kit,respectively.Results VES both in oral and ip.can decrease the development of B(a)P-induced forestomach cancer in mice.While the activity of EROD,phase Ⅰ pharmacological metabolism enzyme,in the VES group(39.1±3.05),were decreased significantly( P <0.01),compared with the B(a)P group(57.9±3.16).Conclusion VES can decrease the carcinogenesis of forestomach cancer in mice involving the depressing activities of EROD.