txnip在uuo小鼠肾间质纤维化中的作用

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1、授予单位代码10089学号或申请号HebeiMedicalUniversity硕士学位论文科学学位TXNIP在UUO小鼠肾间质纤维化中的作用作者姓名：安洋导师：史永红教授专业：病理学与病理生理学二级学院：基础医学院2015年03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究成果，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、公开和使用。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

2、验材料、原始数据、申报的专利等知识产权均归河北医科大学所有。否则，承担相应法律责任。研究生签名：导师签章：逆永化二级学院领导盖章年/P-呷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究工作及取得的研究成果，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。年玄月j曰目录中文摘要································································

3、·············1英文摘要·············································································4英文缩写·············································································7研究论文TXNIP在UUO小鼠肾间质纤维化中的作用前言··················································

4、···························8材料与方法····································································9结果·············································································15附图······································································

5、·······16附表·············································································16讨论·············································································19结论·············································································26参考文

6、献·······································································26综述TXNIP在疾病中的作用及调节机制····································29致谢···················································································38个人简历·································

7、············································39中 文 摘 要TXNIP在UUO小鼠肾间质纤维化中的作用摘要目的：肾脏间质纤维化是各种肾脏病变进展到慢性肾衰竭的共同过程，其主要特征是肾脏内固有细胞纤维化以及细胞外基质蛋白的异常堆积。多种分子机制及信号通路参与其进程，包括TGF-β1激活、肾小管上皮细胞的向间充质细胞转化、细胞外基质包括纤维连接蛋白、胶原(I,III,IV,V和VII型)等的堆积，发挥了重要的作用。硫氧还蛋白相互作用蛋白（thioredoxinin

8、teractingprotein,TXNIP）是一种硫氧还蛋白（thioredoxin，TRX）的内源性抑制蛋白，能够通过与其结合抑制其功能。有研究显示，在高糖诱导的HK-2细胞中，敲低TXNIP能够增加的TRX活性，从而抑制高糖诱导的氧化应激，抑制小管细胞TGF-β信号通路的激活，下调纤维连接蛋白（fibronectin，FN）的表达。在高糖诱导的系膜细胞中，敲低TXNIP能够抑制高糖诱导的纤连蛋白表达。新近的一项研究显示，