敌敌畏对肝脏细胞色素P450含量及活性水平的影响

Effect of dichlorvos on the total content and activity of CYP450 in mice liver

目的观察敌敌畏对小鼠肝脏组织的细胞色素P450(CYP450)含量和氨基比林-N-去甲基化酶活性水平影响,探讨CYP450在敌敌畏代谢中的作用。方法雄性小鼠16只,随机分成诱导组和对照组,诱导组按10mg/kg腹腔注射敌敌畏,对照组注射生理盐水,每2d一次。14d后处死,分别测定肝脏组织的CYP450含量、氨基比林-N-去甲基化酶活性水平,并测定血清丙氨酸氨基转移酶(ALT)活性。结果小鼠经过14d的敌敌畏诱导后,两组肝脏CYP450的含量无统计学意义(P>0.05);氨基比林-N-去甲基化酶的活性水平在敌敌畏诱导组明显高于对照组(P<0.05),两组肝脏的ALT无显著统计学意义(P>0.05)。结论低剂量的敌敌畏不引起肝脏功能的损害,肝脏CYP450虽然没有直接参与敌敌畏的代谢且不影响CYP450含量,但氨基比林-N-去甲基化酶活性水平的增加提示部分CYP450参与敌敌畏的中间代谢产物代谢。

Objective To study the total content and activity of cytochrome P450 （CYP450） in mice liver induced by dichlorvos, and to understand the role of CYP450 in the biotransformation of dichlorvos. Methods Male mouse in induced group were administrated dichlorvos （10 mg/kg, ip）, one injection in every two days, control group were administrated the same dose of saline. After 14 days, The total content of CYP450 and the activity of aminopyrlne-N-demethylase were determined in liver, alanine aminotransferase （ALT） was studied in serum. Results Comparing dichlorvos-induced mouse with the control group, The total content of CYP450 was no difference（P 〉0.05）, and the activity of aminopyrine-N- demethylase was significantly increased in liver （21.17 IU/mg pro vs 15.49, P 〈 0.05）. The activity of ALT did not elevated in two groups （P）0.05）. Conclusion The results presented herein indicate that mice dosed intraperitoneally with low dose dichlorvos show no effect on the total content of hepatic CYP450 and no damage in liver, and suggest that some isoforms of CYP450 may participate in some metabolites of dichlorvos.