foxo3a信号在纳米二氧化钛气管暴露致大鼠dna损伤中的作用研究

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1、授予单位代码10089_学号或申请号20122585HebeiMedicalUniversity硕士学位论文科学学位F0X03a信号在纳米二氧化钛气管暴露致大鼠DNA损伤中的作用研究研究生：朱越导师：张荣教授专业：卫生毒理学二级学院：公共卫生学院2015年3月河北医科大学学位论文使用授权及知识产权归属承诺本学位论文在导师（或指导小组）的指导下，由本人独立完成。本学位论文研究所获得的研宄成果，其知识产权归河北医科大学所有。河北医科大学有权对本学位论文进行交流、公幵和使用。凡发表与学位论文主要内容相关的论文，第一署名为单位河北医科大学，试验材料、原始数据、申报的专利等知识产权均归河北医

2、科大学所有。否则，承担相应法律责任。Z：：丨,/i'j'”‘,研究生签名：_导师签章：名、二级学_领导盖章;.如i:年j月如日河北医科大学研究生学位论文独创性声明本论文是在导师指导下进行的研宄工作及取得的研宄成果，除了文中特别加以标注和致谢等内容外，文中不包含其他人已经发表或撰写的研究成果，指导教师对此进行了审定。本论文由本人独立撰写，文责自负。研究生签名：舞絶导师签章:参、jo^年》月％曰目录中文摘要··············································································1英文摘要·······

3、·······································································5英文缩写··············································································10研究论文FOXO3a信号在纳米二氧化钛气管暴露致大鼠DNA损伤中的作用研究前言··············································································11材料与方法··············

4、·······················································12结果··············································································22附图··············································································26附表·······································································

5、·······38讨论··············································································42结论··············································································46参考文献········································································47综述纳米二氧化钛的体内代谢分布和氧化损伤作用·····················

6、·50致谢·····················································································60个人简历··············································································61中文摘要FOXO3a信号在纳米二氧化钛气管暴露致大鼠DNA损伤中的作用研究摘要目的：纳米二氧化钛(Nanoparticletitaniumdioxide，Nano-TiO2)具有优异的物理和化学性质，被广泛用于医药、废水处理、涂料、杀菌

7、、化妆品、食品添加剂、生物医用陶瓷等领域。纳米颗粒主要通过呼吸道、皮肤接触和消化道进入人体，造成健康危害，其中吸入是最常见的暴露途径之一。Nano-TiO2表面具有较高的化学反应性，形成大量的自由基，作用生物体后可引起氧化应激，使活性氧(Reactiveoxygenspecies，ROS)生成增多，破坏DNA碱基和磷酸骨架，造成DNA损伤。Nano-TiO2造成的氧化应激与其毒性高度相关，但其作用靶点和调控机制尚不清楚。本文通过气管灌注方法，模拟呼吸道吸收途径，观察N