摘要
目的:探索维生素E(VE)对青春期邻苯二甲酸二异辛酯(DEHP)暴露致雄性大鼠生殖毒性的干预作用以及其机制。方法:将30只35日龄雄性SD大鼠(体重96~122 g)随机分为对照组(玉米油),低[10 mg/(kg·d)]、中[100 mg/(kg·d)]、高[500 mg/(kg·d)]DEHP组,以及VE干预组[(500 mg/(kg·d)DEHP+100 mg/(kg·d)VE],各组给予相应食物30 d。在染毒干预结束后,分别检测大鼠睾丸组织氧化应激指标、附睾尾部精子参数、血清生殖激素水平、凋亡相关靶基因及蛋白的表达。结果:与对照组比较,中、高DEHP组血清中FSH、LH和T水平明显降低,精子运动参数VAP、VCL明显降低,SOD和GSH-Px活力显著降低,Bak、Bax基因表达和Bax/Bcl-2基因表达比值显著升高,细胞色素C mRNA表达及细胞色素C和Caspase-3蛋白表达均显著上调(P均<0.05);高DEHP组MDA含量[(3.32±0.87)nmol/mg pro vs(2.13±0.49)nmol/mg pro]明显升高,精子运动参数VAP、VCL、VSL、STR、LIN、WOR均明显降低(P<0.05)。与高DEHP组比较,VE干预组的LH和T水平明显升高;VAP、VSL、VCL、STR和WOB明显升高;SOD和GSH-Px活力显著升高;MDA含量明显降低;Bak、Bax基因表达和Bax/Bcl-2基因表达比值显著降低;细胞色素C、Caspase-3 mRNA表达及蛋白表达均显著下调(P均<0.05)。结论:青春期DEHP暴露可抑制生殖激素分泌或释放,导致雄性大鼠睾丸组织氧化损伤,激活细胞线粒体凋亡通路,也可导致附睾精子质量下降;而VE对DEHP所诱导的雄性生殖毒性具有一定的拮抗作用。
Objective： To explore the antagonistic effect of vitamin E（ VE） on male reproductive toxicity induced by di-2-ethylhexyl phthalate（ DEHP） in pubertal SD rats and its underlying mechanisms. Methods： Thirty 5-week-old male SD rats were randomly divided into five groups of equal number,corn oil control,low-dose（ 10 mg/kg/d）,medium-dose（ 100 mg/kg/d） and high-dose DEHP exposure（ 500 mg/kg/d）,and VE intervention（ high-dose DEHP ＋ VE [100 mg/kg/d]）,and treated respectively for 30 successive days. At 3 days after treatment,the testes of the animals were harvested for determination of the oxidative stress index,serum reproductive hormone levels,cauda epididymal sperm parameters,and expressions of cell apoptosis-related genes and proteins. Results： Compared with the control group,the rats of the medium-and high-dose DEHP groups showed significant decreases in the levels of such serum reproductive hormones as follicle-stimulating hormone（ FSH）,luteinizing hormone（ LH） and testosterone（ T）,sperm parameters as average path velocity（ VAP）,straight line velocity（ VSL）,curvilinear velocity（ VCL）,straightness（ STR）,linearity（ LIN） and wobble（ WOB）,and the activities of superoxide dismutase（ SOD） and glutathione peroxide（ GSH-Px）,but significant increases were observed in the latter two groups in the content of malondialdehyde（ MDA）（ [3. 32 ± 0. 87] nmol/mg pro vs [2. 13 ± 0. 49] nmol/mg pro）,mRNA expressions of Bad,Bax,Cytochrome C,Caspase-3 and the Bax/Bcl-2 ratio,and protein expressions of Cytochrome C and Caspase-3. In comparison with the high-dose DEHP group,the VE intervention group exhibited remarkably increased serum LH and T levels,sperm VAP,VSL,VCL,STR and WOB,and activities of SOD and GSH-Px,but markedly decreased mRNA expressions of Bad,Bax,Cytochrome C,Caspase-3 and the Bax/Bcl-2 ratio as well as the protein expressions of Cytochrome C and Caspase-3 in the testis tissue（ P〈0. 05）. Conclusion： Exposure to DEHP induces androgen secretion disorders,causes oxidative damage to the testicular tissue,activates the mitochondrial apoptosis pathway in the testis,and ultimately reduces the quality of epididymal sperm,while VE can protect the rat testis from DEHP-induced reproductive toxicity.
作者
王超云
张娟娟
段鹏
WANG Chao-yun;ZHANG Juan-juan;DUAN Peng(Center of Reproductive Medicine, Taihe Hospital of Shiyan / The Affiliated Hospital of Hubei Medical University, Shiyan , Hubei 442000, China;Family Planning Research Institute, Tongii Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China;Faculty of Preventive Medicine, School of Public Health and Its Management, Hubei Medical University, Shiyan, Hubei 442000, China)
出处
《中华男科学杂志》
CAS
CSCD
北大核心
2018年第7期589-595,共7页
National Journal of Andrology
基金
中国博士后基金项目(2016M602310)
湖北医药学院博士启动金项目(2017QDJZR07)~~
作者简介
王超云（1973-），女，湖北十堰市人，主管护师，本科，从事不孕不育的临床及基础研究。;通讯作者：段鹏，Email：meduanpeng@163．com
