增塑剂DIDP对肝脏氧化应激损伤及VitE拮抗作用研究  

Hepatic Oxidative Stress Injury Induced by Plasticizer DIDP and the Antagonism of VitE

作　　者：李崇尧 陈莹莹 宋鹏 雷璠 武阳 晏彪 马萍 Li Chongyao;Chen Yingying;Song Peng;Lei Fan;Wu Yang;Yan Biao;Ma Ping(College of Pharmacy,Hubei University of Science and Technology,Xianning 437100,China;Laboratory of Environment-Immunological and Neurological Diseases,Research Center of Basic Medical Sciences,Hubei University of Science and Technology,Xianning 437100,China)

机构地区：[1]湖北科技学院药学院,咸宁437100 [2]湖北科技学院基础医学院,环境-免疫与神经系统疾病实验室,咸宁437100

出　　处：《生态毒理学报》2019年第6期170-178,共9页Asian Journal of Ecotoxicology

基　　金：湖北省高等学校优秀中青年科技创新团队计划项目(T201717);湖北省卫生计生委重点支撑项目(WJ2017Z027);湖北省卫生计生委面上项目(WJ2019M093)。

摘　　要：研究增塑剂邻苯二甲酸二异癸酯(didecyl phthalate, DIDP)致雄性小鼠肝损伤作用及其机理。以雄性BALB/c小鼠为受试动物,随机分为7组,包括溶剂对照组(生理盐水)、4个DIDP染毒组(0.15、1.5、15和150 mg·kg-1)、维生素E(vitamin E, VitE)(100 mg·kg-1)处理组和DIDP+维生素E处理组(150 mg·kg-1DIDP+100 mg·kg-1VitE),连续灌胃14 d。以肝组织匀浆测定活性氧(reactive oxygen species, ROS)、还原型谷胱甘肽(glutathione, GSH)、丙二醛(malondialdehyde, MDA)和细胞凋亡因子半胱氨酸天冬氨酸蛋白酶3(cysteine aspartic proteinase 3, Caspase-3)水平。采用动物自动生化分析仪检测肝功能指标血清中丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase, AST)、白蛋白(albumin, ALB)水平,并同时观察肝组织的病理变化与荧光染色结果。随着DIDP染毒剂量的增加,小鼠肝组织ROS、MDA和Caspase-3含量逐渐上升,血清ALT和AST水平也逐渐上升,GSH含量逐渐降低,血清ALB水平也逐渐降低,差异具有统计学意义(P <0.05,P <0.01);VitE处理组ROS、MDA和Caspase-3含量相应降低,血清ALT和AST水平也相应降低,GSH含量逐渐上升,血清ALB水平也相应上升。小鼠肝组织形态观察结果表明,随着DIDP染毒剂量的增加,小鼠肝组织的病理损伤程度呈上升趋势。研究表明,较高剂量(≥15 mg·kg-1)的DIDP能造成小鼠的肝脏损伤与细胞凋亡,抗氧化剂VitE可使肝脏损伤与细胞凋亡减轻,对小鼠肝组织起保护作用,说明氧化应激介导了DIDP对机体的损伤。This study investigates the oxidative damage induced by plasticizer diisodecyl phthalate(DIDP) on male mouse liver tissue. BALB/c mice are randomly dividied into seven groups and orally administered with drugs daily for fourteen days;the groups are one solvent control group(saline), four diisodecyl phthalate groups, one vitamin E(100 mg·kg-1) group and one vitamin E treatment group(150 mg·kg-1 DIDP+100 mg·kg-1 VitE). Exposure doses of diisodecyl phthalate groups are 0.15, 1.5, 15 and 150 mg·kg-1 respectively. The content of reactive oxygen species(ROS), reduced glutathione(GSH), malondialdehyde(MDA) and cysteine aspartic proteinase 3(Caspase-3) in liver tissue homogenate are detected repectively. Animal autonomic biochemical analyzer is utilized to detect serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), and albumin(ALB) to evaluate liver function.Meanwhile, pathological changes and fluorescent staining results of liver tissue are observed. With the increase of DIDP exposure dose, the contents of ROS, MDA and Caspase-3 in liver tissue of DIDP exposed group increased gradually, serum ALT and AST levels also increased gradually, GSH content decreased gradually, serum ALB level also decreased gradually, and the difference is statistically significant(P <0.05,P <0.01). ROS, MDA and Caspase-3 decreased in the VitE treatment group, serum ALT and AST levels also decreased, GSH content increased gradually, and serum ALB level also increased. The morphology of liver tissue in male mice indicated that the degree of pathological damage of mouse liver tissue was on the rise with the increase of DIDP dose. The results show that higher dose(≥15 mg·kg-1) of DIDP can cause liver damage and apoptosis in mice. The antioxidant VitE can effectively protect the liver tissue, make liver damage and apoptosis alleviated.

关 键 词：邻苯二甲酸二酯异癸酯 活性氧 还原型谷胱甘肽 丙二醛 半胱氨酸天冬氨酸蛋白酶3 血清丙氨酸氨基转移酶 天门冬氨酸氨基转移酶 白蛋白 

分 类 号：X171.5[环境科学与工程—环境科学]