tlr4及相关炎症因子在糖尿病大鼠心脏、肝脏和肾脏中的表达

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1、授予单位代码10089_学号或申请号12068K^^ASHebeiMedicalUniversity硕士学位论文在职科学学位TLR4及相关炎症因子在糖尿病大鼠心脏、肝脏和肾脏中的表达学位申请人：王丽霞导师：尹晓琳教授专业：免疫学二级学院：基础医学院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

2、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科大学所有。否则,承担相应法律责任。研究生签名：导师签章:级学院领导盖章：年月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。研究生签名：；佛导师签章：目录中文摘要·······························································

3、··············1英文摘要·············································································4研究论文TLR4及相关炎症因子在糖尿病大鼠心脏、肝脏和肾脏中的表达前言·············································································8材料与方法·················································

4、···················9结果·············································································11附图·············································································13讨论·············································································18结

5、论·············································································19参考文献·······································································20综述TLRs在糖尿病及其并发症炎症反应中的作用·······················23致谢·························································

6、··························36个人简历·············································································37中文摘要TLR4及相关炎症因子在糖尿病大鼠心脏、肝脏和肾脏中的表达摘要目的：糖尿病（diabetemellitus，DM）是一种常见病，其常见的并发症主要发生在微血管和大血管，如糖尿病肾病、视网膜病、冠心病等。是糖尿病致伤、致残的主要原因。目前对并发症发病机制的研究较多，但近些年慢性炎症反应在并发症中的作

7、用受关注。其中TLR4（Toll1ikereceptor4，TLR4)这一普遍存在于多种免疫细胞的模式识别受体介导的炎症激活可能与DM并发症中的炎症反应有关。已知TLR4表达于巨噬细胞等固有性免疫细胞表面，糖尿病发生时，其内源性配体如热休克蛋白60（HSP60）、高迁移率族蛋白1（HMGBI）增加，可激活TLR4，诱导炎症反应。且我们前期临床和实验研究中均证实高糖状态下多种细胞TLR4的表达显著升高，与其相关的炎症因子IL-1β和TNF-α等的表达也升高，但是TLR4在其它脏器的表达及其相关炎症因子的作用尚未完全清楚。因此

8、，本课题拟制备DM大鼠模型，测定不同组织如肝脏、心脏和肾脏的TLR4及其相关炎症因子IL-1β和TNF-α的表达，以及大鼠各组织炎症浸润的状态，全面了解DM状态下多脏器的炎症反应状态，进一步探讨DM的并发症的发生机制，为DM并发症的抗炎治疗提供实验依据。方法：1制备糖尿病大鼠模型：SD雄性大鼠腹腔注射S