Hepcidin、铁和炎症相互关系的初步研究

发布时间：2018-01-27 02:29

本文关键词： 抗菌肽刺激抑菌　出处：《浙江大学》2011年硕士论文　论文类型：学位论文

【摘要】：Hepcidin是一种抗菌肽,也是重要的铁调素分子。在高等脊椎动物中研究发现它不仅能直接抑制细菌生长,还可以调控机体的铁代谢平衡。它既在机体天然免疫中发挥作用,又在机体内环境稳定中担当角色,是一个重要的界面分子。Hepcidin的表达受多种因素影响,炎症反应就是其中之一。本论文我们以CpG刺激斑马鱼来构建炎症反应模型,研究Hepcidin、铁和炎症之间的相互关系。研究过程中我们用CpG-ODN、含CpG重复基元的pYES质粒和嗜水气单胞菌(Aeromonas hydrophila)基因组DNA刺激斑马鱼,利用RT-PCR和荧光定量PCR检测刺激前后Hepcidin表达的变化,统计斑马鱼在含CpG质粒预刺激再感染嗜水气单胞菌后的死亡率,并进一步检测斑马鱼血清中Hepcidin及铁含量的变化,同时初步探索了这两者以及补体的变化对机体抗细菌感染能力的影响。研究结果显示CpG刺激后斑马鱼肝脏Hepcidin mRNA表达上调；嗜水气单胞菌感染后的存活率显著提高；血清中Hepcidin浓度提高,但血清中的铁含量下降；血清抑制细菌生长的能力和Hepcidin、铁还有补体有关。研究表明炎症发生时Hepcidin表达上调,而血清铁含量下降,进而抑制细菌生长,从而抑制体内的炎症反应,这是宿主体内一种抑制细菌感染的新机制,研究结果为深入探讨Hepcidin在机体中的抑菌机制打下基础。
[Abstract]:Hepcidin is an antimicrobial peptide and an important iron modulin molecule. Studies in higher vertebrates have found that it not only directly inhibits bacterial growth. It can also regulate the balance of iron metabolism in the body. It not only plays a role in the innate immunity of the body, but also plays a role in the stability of the body environment. Inflammatory response is one of the most important interfacial molecules, and inflammatory response is one of them. In this paper, we use CpG to stimulate zebrafish to construct inflammatory response model. To study the relationship between hepcidin, iron and inflammation. We used CpG-ODN in the course of the study. Zebrafish were stimulated by pYES plasmid containing CpG repeats and Aeromonas hydrophila genomic DNA. The changes of Hepcidin expression before and after stimulation were detected by RT-PCR and fluorescence quantitative PCR, and the mortality of zebrafish after pre-stimulation with CpG plasmid and re-infection with Aeromonas hydrophila was analyzed. The changes of Hepcidin and iron in zebrafish serum were further determined. At the same time, the effects of these two and the changes of complement on the ability of anti-bacterial infection were preliminarily explored. The results showed that the expression of Hepcidin mRNA in the liver of zebrafish was up-regulated after CpG stimulation. The survival rate of Aeromonas hydrophila was significantly increased after infection. The concentration of Hepcidin in serum increased, but the content of iron in serum decreased. The ability of serum to inhibit bacterial growth is related to hepcidin, iron and complement. Studies have shown that Hepcidin expression is up-regulated and serum iron content is decreased during inflammation, which inhibits bacterial growth and thus inhibits the inflammatory response in vivo. This is a new mechanism to inhibit bacterial infection in the host. The results lay a foundation for the further study of the bacteriostatic mechanism of Hepcidin in the organism.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363

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