团头鲂IL-6介导的JAK/STAT信号通路在细菌感染-铁代谢互作中的作用机制

细菌性败血症为淡水鱼类的主要病害之一，严重影响水产养殖业的健康发展。前期研究表明细菌感染后鱼类铁代谢途径的免疫功能被激活，其可能由IL-6介导的JAK/STAT信号通路调控，该通路参与人类多种疾病的发病过程是治疗的靶标，而在鱼类中的研究极为匮乏。本项目拟在前期研究基础上，以团头鲂为研究对象，采用生物信息学、Western blot、qRT-PCR、免疫组化、RNAi、ChIP等技术手段，系统比较研究鱼类JAK/STAT信号通路成员并确定关键成员；采用IL-6/JAK/STAT激活/抑制干预方式，综合分析肝组织或细胞中JAK与STAT活性、各炎症因子和铁代谢基因表达、铁含量及分布、组织/细胞学变化等，探讨JAK/STAT通路对上游炎症因子的反馈和下游铁代谢的影响，阐明此信号通路在炎症-铁代谢crosstalk中的作用机制。结果将丰富鱼类抗病分子机制的理论知识，为鱼类抗病分子育种提供新的视角。

Bacterial septicemia is one of the main diseases of freshwater fish, which seriously affects the healthy development of aquaculture. Previous studies have shown that the immune function of fish iron metabolism pathway is activated after bacterial infection, which may be activated by the IL-6 mediated JAK/STAT signal pathway. JAK/STAT is involved in the pathogenesis of a variety of human diseases and is the target of treatment, but there is a lack of research in fish. Based on the previous studies, taking Megalobrama amblycephala, one of the freshwater fish, as the research object, this project aims to systematically compare and study fish JAK/STAT signaling pathway by using bioinformatics, Western blot, qRT-PCR, immunohistochemistry, RNAi, ChIP and other technical means. Using IL-6/JAK/STAT activation/inhibition intervention approach, the JAK and STAT activity, expression of inflammatory factors and iron metabolism related genes, iron content and distribution, tissue/cytological changes in the liver tissue or cells are analyzed, to investigate the feedback and effects of JAK/STAT pathway on upstream inflammatory factors and downstream iron metabolism, and to elucidate the mechanism of JAK/STAT pathway in inflammatory-iron metabolism crosstalk. The results will enrich the theoretical knowledge of molecular mechanisms of fish disease resistance and provide a new perspective for fish disease resistance molecular breeding.