邻苯二甲酸二丁酯和邻苯二甲酸二(2-乙基己基)酯联合染毒对雄性大鼠肝脏P450酶的影响

Effects of co-exposure of DBP and DEHP on cytochrome P540 enzyme activity in male rat liver

目的探讨邻苯二甲酸二丁酯(DBP)和邻苯二甲酸二(2-乙基己基)酯(DEHP)联合染毒对雄性大鼠肝脏P450酶的影响。方法将20只健康清洁级成年SD雄性大鼠随机分为4组,分别为阴性对照(玉米油)组、DBP(1/20LD50,1.0g/kg)染毒组、DEHP(1/20LD50,1.7 g/kg)染毒组和DBP(1.0 g/kg)+DEHP(1.7 g/kg)染毒组,每组5只。采用灌胃方式进行染毒,每天1次,连续染毒7 d。末次染毒24 h后测定细胞色素P450酶总活力、CYP1A1活力、CYP2E1活力、CYP3A活力。结果 DBP和DEHP联合染毒可使肝脏脏器系数升高,交互作用均有统计学意义(P<0.05),表现为协同作用;均可诱导上述4种酶活力增加,对肝细胞色素P450酶总活力、CYP1A1活力、CYP3A均存在协同作用(P<0.05);对CYP2E1活力存在拮抗作用(P<0.05)。结论 DBP和DEHP联合染毒对雄性大鼠肝脏P450酶存在交互作用。

Objective To study the combined toxic effects of di-n-butyl phthalate （DBP） and di-2-ethylhexyl phthalate（DEHP） on cytochrome P540 enzyme activity in male rat liver. Methods Twenty healthy and clean adult male SD rats were randomly divided into four groups, control group （given coin oil）, DBP group （1/20LD50, 1.0 g/kg,dissolved in coin oil）, DEHP group （1/20 LD50,1.7 g/kg,dissolved in coin oil） and DBP （1.0 g/kg）＋ DEHP （1.7 g/kg）, five rats in each group, the treatments were conducted through gavage, once a day, for seven consecutive days. The activities of cytochrome 17450 and CYP1A1,2E1,3A were assessed in liver 24 h after the last exposure. Results DBP and DEHP obviously induced an increase in the liver organ body weight ratio （P〈0.05）,there was synergism between DBP and DEHP on the liver organ body weight ratio. DBP and DEHP induced increases in these four kinds of enzyme activity, there was synergism on the activities of cytochrome P450,CYP1A1 and CYP3A in the liver （P〈0.05）, there was antagonism on the activity of CYP2E1 in the liver （P〈0.05）. Conclusion In the present study, interaction was seen between DBP and DEHP on the activities of cytochrome P450, CYP1A1,CYP2E1 and CYP3A in the liver of rats.