干扰素γ介导噬血细胞综合征血细胞减少的机制研究

噬血细胞综合征(HPS)是一组因免疫功能异常导致的过度炎症反应，外周血细胞减少是该病最主要的特点。本课题组研究发现进行性难以纠正的全血细胞减少与不良预后密切相关。有效改善外周血细胞水平状态，缩短血细胞减少持续时间是治疗的关键环节。血清干扰素γ(IFN-γ)水平与血细胞减少存在相关性，预实验结果提示其可能影响CD34+细胞的分化，使血细胞生成减少，并介导巨噬细胞活化产生噬血现象加速血细胞消耗。为证实这一假说，本课题拟通过体外细胞培养及动物体内试验，采用流式细胞术、免疫组化、酶联免疫吸附试验及免疫印迹方法，首先将CD34+细胞体外培养，观察IFN-γ对其分化的影响；其次在基因缺陷小鼠模型中观察IFN-γ对血细胞数量的影响，并鉴定巨噬细胞功能以及IFN-γ受体信号传导通路。上述研究旨在阐明IFN-γ介导HPS血细胞减少的病理生理机制，为指导临床用药，探索治疗新方法提供理论依据。

Hemophagocytic syndrome (HPS) is a group of immune dysfunction caused by excessive inflammation, and reduction of peripheral blood cells is the most important characteristic of the disease. Our research group found that difficult correction of progressive pancytopenia is closely related with poor prognosis. Thus, effectively improving the state of the level of peripheral blood cells, shortening the duration of the reduction of blood cells is a key part of treatment. The level of serum interferon-γ (IFN-γ) is correlate with the reduction of blood cells. The pre-experimental results prompted it may affect the differentiation of CD34+ cells, which decreased the production of blood cells and mediated macrophage activation to generate hemophagocytic phenomenon and then accelerate consumption of blood cells. The subject is to be adopted by cell growth in vitro culture and in vivo studies which using flow cytometry, immunohistochemistry, enzyme-linked immunosorbent assay and Western blot method to confirm this hypothesis. Initially CD34+ cells are cultured in vitro and observe the impact of IFN-γ on cell differentiation; then observe of the effect of IFN-γ on the number of blood cells in gene-deficient mice model and the identify the function of macrophage and the signal transduction pathways of IFN-γ receptor. The above study is designed to clarify the pathophysiology of IFN-γ-mediated cytopenia of HPS and provide a theoretical basis for exploring the new clinical treatment.