邻苯二甲酸二(2-乙基己基)酯对小鼠肾脏损害及氧化应激机制的研究  

Diethylhexyl phthalate induced oxidative stress and renal toxicity in mice

作　　者：方鑫[1] 李海玲[1] 胡月玲[1] 迟宝峰[1] 戴红[1] 

机构地区：[1]内蒙古医科大学公共卫生学院,内蒙古呼和浩特010059

出　　处：《中国预防医学杂志》2014年第1期8-12,共5页Chinese Preventive Medicine

基　　金：内蒙古科技厅科技项目(2012MS1146)

摘　　要：目的研究邻苯二甲酸二(2-乙基己基)酯(DEHP)的肾脏毒性及氧化应激损伤作用机制;探讨相关影响因素。方法建立小鼠DEHP肾损伤模型:选择昆明4周龄小鼠60只,体重(20±2)g,雌雄各半,随机分为6组,每组10只。O组为空白对照组,A组给予DEHP 750 mg/kg,B组给予DEHP1 500mg/kg,C组给予3 000mg/kg DEHP+10%维生素C,D组给予DEHP 3 000 mg/kg,E组给予3 000mg/kg DEHP+0.5%尼古丁;经食饵和饮水连续自然给食染毒,于染毒第4周末处死。测量小鼠肾脏和体质量的变化,检测不同DEHP染毒剂量组小鼠的血液、肾脏中谷胱甘肽过氧化物酶(GPX)、过氧化氢(H2O2),丙二醛(MDA)等变化。将实验数据进行单因素方差分析(ANOVA)。结果随着DEHP染毒剂量的增加,小鼠体质量逐渐降低(P<0.05),高剂量组肾脏脏器系数呈现增加趋势。DEHP高剂量组HE染色可见肾脏组织出现以明显充血和水肿为主的损伤,尼古丁干扰组最为严重。维生素C呈现良好的肾脏保护作用。氧化应激相关物质的改变:血液中的GPX活性由对照组的(471.32±120.24)U/ml降低至E组的(208.75±52.92)U/ml(P<0.05),且有剂量-反应关系;肾脏中GPX活性降低(P<0.05),同时肾组织中H2O2含量由(407.74±328.83)mmol/mg蛋白增加到(1 674.98±376.07)mmol/mg蛋白(P<0.05),血液中H2O2含量也随着DEHP的剂量增加而增加(P<0.05);肾组织中MDA含量增加(P<0.05);同时维生素C的保护作用和尼古丁的协同作用也有体现。结论 DEHP具有小鼠肾脏毒性,其作用机制可能与氧化应激有关,抗氧化剂维生素C对DEHP所致肾脏损伤具有抑制作用。Objective To explore the mechanisms of oxidative stress and renal toxicity induced by diethylhexyl phthalate （DEHP） in mice. Methods Sixty Kunming mice were randomly divided into 6 groups （n = 10） and were fed with 750 mg/kg DEHP, 1500 mg/kg DEHP, 3000 mg/kg DEHP plus 10% Vitmin C, 3 000 mg/kg DEHP, 3 000 mg/kg DEHP plus 0.5% nicotine and water as control for 4 weeks. Then, mice body weight was measured, blood samples and kidneys were collected to determine the activities of GPX, as well as the contents of H2O2 and MDA. ANOVA was used for data analysis. Results The average body weight de creased with an increased amount of DEHP exposure （P〈0.05） . Meanwhile, severe renal injury character ized by congestion and edema was observed in mice fed with high dose of DEHP, especially when nicotine was given. Whereas, vitmin C could alleviate the renal damage. Both blood and kidney GPX activities decreased significantly in mice exposed to high dose of DEHP compared to control mice （P〈0.05）, while, in kidney, the contents of H2 O2 and MDA, as well as H2O2 in blood all elevated along with increased dose of DEHP exposure （P〈0.05） . Conclusions DEHP induced renal toxicity is closely associated with oxidative stress in mice and this injury can be reduced by. antioxidant vitamin C.

关 键 词：邻苯二甲酸二(2-乙基己基) 酯(DEHP) 肾脏毒性 氧化应激 

分 类 号：R114[医药卫生—卫生毒理学]