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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 investigate the effects of DBP and DEHP on the liver P450 enzymes in male rats. Methods Twenty male SD rats were randomly divided into 4 groups: negative control (corn oil), DBP (1 / 20LD50, 1.0g / kg), DEHP g / kg) and DBP (1.0 g / kg) + DEHP (1.7 g / kg). Gavage by way of exposure, 1 times a day, continuous exposure 7d. The cytochrome P450 enzyme activity, CYP1A1 activity, CYP2E1 activity and CYP3A activity were measured 24 h after the last exposure. Results The combination of DBP and DEHP could increase the coefficient of liver organ, the interaction was statistically significant (P <0.05), showing a synergistic effect; all of them could induce the above four enzymes to increase their activity and inhibit the activity of hepatocyte cytochrome P450 Total activity, CYP1A1 activity and CYP3A had synergistic effect (P <0.05), but antagonized the activity of CYP2E1 (P <0.05). Conclusion DBP and DEHP combined treatment of male rat liver P450 enzyme interaction.