二硫化碳对雄性大鼠生殖功能的影响及MPTP的干预作用  

Effects of carbon disulfide on reproductive function in male rats and intervention of MPTP

作　　者：董煜[1,2] 郭寅生[2] 王为[2] 张振[2] 周义军[3] 黄晓彧[2] 陈国元[2] 

机构地区：[1]西安市疾病预防控制中心,陕西西安710054 [2]华中科技大学同济医学院公共卫生学院,湖北武汉430030 [3]上海交通大学公共卫生学院,上海200025

出　　处：《工业卫生与职业病》2016年第3期176-181,共6页Industrial Health and Occupational Diseases

基　　金：国家自然科学基金资助项目(编号:81172637)

摘　　要：目的观察二硫化碳(CS2)对雄性大鼠生殖功能的影响及初步探讨线粒体通透性转换孔(mitochondrial permeability transition pore,MPTP)在这种改变中所起的作用。方法 48只SD雄性大鼠随机分为6组:前4组为单纯CS2染毒组,染毒浓度分别为0、50、250、1 250mg/m3,第5、6组CS2染毒浓度均为1 250mg/m3,采取静式吸入染毒方式,2h/d,5d/周,共10周。染毒4周后,第5、6两组在给予染毒的同时分别以浓度12.5mg/kg环孢素A(Cyclosporine A,CsA,MPTP抑制剂)和25mg/kg氯尼达明(Lonidamine,LND,MPTP开放剂)进行灌胃,1次/d,5d/周,共6周。染毒结束后,检测大鼠精子指标,透射电镜观察生殖细胞超微结构的改变,同时检测MPTP干预剂的干预作用。结果随着CS2染毒浓度的增加,各组大鼠体质量,睾丸、附睾脏器系数,精子总数等呈现不同程度的降低,尤以高浓度组明显(P<0.05),精子畸形率则高于对照组(P<0.05)。各染毒组线粒体膜电位下降的细胞比例与对照组相比均明显增加(P<0.05)。电镜结果显示,CS2染毒可造成生殖细胞线粒体嵴减少或消失,线粒体发生肿胀、形成空泡。抑制剂CsA对CS2导致的生殖细胞毒性有一定的拮抗作用,而开放剂LND则进一步加剧病变的发生。结论不同浓度CS2染毒可以造成雄性大鼠不同程度生殖功能障碍,MPTP在此过程中发挥重要作用。Objective To observe the reproductive toxicity of carbon disulfide and explore the role of MPTP.Methods Forty-eight Sprague Dawley male rats were randomly divided into six groups：four groups treated with varying levels of CS2 concentration（0,50,250,1250 mg/m3）;a 1250 mg/m3 CS2 ＋Cyclosporine A（CsA,one type of MPTP inhibitor）group and a 1250mg/m3 CS2 ＋ Lonidamine（LND,one type of MPTP opener）group.Five experimental groups were treated with CS2 by inhalation for 10weeks（ws）,2h/d,5d/w.After 4 ws,the two intervention groups were treated with CsA（12.5 mg/kg）and LND（25mg/kg）by gavage,once a day for 6 ws.After 10 ws treatment,we measured sperms of male rats.The transmission electron microscope（TEM）was used to observe the ultrastructure of testis cells of rats.Detect the interventional effect of the intervention agents simultaneously.Results Along with the increase of the concentration of CS2,the body quality,the organ coefficient,the number of sperm and other indicators were all lower than the control group,each parameter between the high group and the control group was statistically significant（P〈0.05）.In contrast,the teratospermia increased compared with the control group（P〈0.05）.The proportion of mitochondrial membrane potential loss cells of all the CS2 exposed groups were significantly increased compared with the control group（P〈0.05）.TEM results showed that CS2 exposure could induce mitochondria cristae decrease or disappear in sperm cells,even swelling and cavitation.CsA significantly protects against on reproductive toxicity in testes of male rats with CS2,while LND strengthen the toxic effects.Conclusions Different concentrations of CS2 can cause reproductive dysfunction in varying aspects,MPTP plays an important role in this process.

关 键 词：二硫化碳 环孢素A 氯尼达明 线粒体通透性转换孔 生殖毒性 睾丸 

分 类 号：R114[医药卫生—卫生毒理学]