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

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ＤＥＨＰ７５０ ｍｇ／ｋｇ，Ｂ 组给予ＤＥＨＰ
１５００ｍｇ／ｋｇ ，Ｃ 组给予３０００ ｍｇ／ｋｇＤＥＨＰ＋１０％ 维生素Ｃ，Ｄ 组给予ＤＥＨＰ３０００ ｍｇ／ｋｇ，Ｅ 组给予
３０００ｍｇ／ｋｇＤＥＨＰ＋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（犘＜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 （犘＜０．０５），且有剂量 反应关系；肾脏中ＧＰＸ 活性降低（犘＜０．０５），
同时肾组织中Ｈ２Ｏ２ 含量由（４０７．７４±３２８．８３）ｍｍｏｌ／ｍｇ蛋白增加到（１６７４．９８±３７６．０７）ｍｍｏｌ／ｍｇ蛋白
（犘＜０．０５），血液中Ｈ２Ｏ２ 含量也随着ＤＥＨＰ 的剂量增加而增加（犘＜０．０５）；肾组织中ＭＤＡ 含量增加（犘
＜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。
关键词：邻苯二甲酸二（２ 乙基己基）酯（ＤＥＨＰ）；肾脏毒性；氧化应激
中图分类号：Ｒ１２　　文献标识码：Ａ　　文章编号：１００９ ６６３９ （２０１４）０１ ０００８ ０５

Diethylhexyl phthalate induced oxidative stress and renal toxicity in mice

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.