循环纤维细胞的类干细胞特性及其在矽肺中的作用、机制与生物标志价值

项目名称： 循环纤维细胞的类干细胞特性及其在矽肺中的作用、机制与生物标志价值

项目编号： No.81472954

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郝长付

作者单位： 郑州大学

项目金额： 85万元

中文摘要： 成纤维细胞/肌成纤维细胞作为矽肺纤维化过程中重要的终端效应细胞受到高度重视。近年研究提示循环纤维细胞具有炎症趋化、类干细胞分化等特性，可能是成纤维细胞/肌成纤维细胞的又一主要来源，但其与矽肺发病的关系尚未见报道。拟建立细胞共培养矽肺体外模型，应用激光共聚焦、电镜、流式细胞术等验证循环纤维细胞的类干细胞特性和多向转化能力，采用高通量芯片、免疫共沉淀等技术探索其表观遗传变化规律，比较其与肺成纤维细胞、肺泡上皮细胞转分化的同异；建立矽尘气溶胶动式染毒动物模型，采用荧光标记、免疫组化、流式细胞术等观察循环纤维细胞在外周血、肺组织中数量、形态变化规律及纤维化组织中肌成纤维细胞的来源分布；通过病例对照调查，检测接尘工人、矽肺病人血液、诱导痰、支气管肺泡灌洗液中循环纤维细胞及相关因子水平，探讨其生物标志价值。研究将为进一步揭示矽肺的发病机制，寻找有效的生物监测、早期诊断指标及潜在的干预靶点提供新的思路。

中文关键词： 循环纤维细胞；干细胞；矽肺；尘肺；二氧化硅

英文摘要： It was attached great importance to fibroblasts/myofibroblasts as important end effector cells in the process of silicosis pulmonary fibrosis. Recent studies had shown that circulating fibrocytes derived from bone marrow could be a major source of fibroblasts / myofibroblasts, which followed the lung fibroblast cells and alveolar epithelial mesenchymal transdifferentiation. Circulating fibrocytes had chemotactic in response to inflammation, and differentiation ability like stem cell. It wsa closely related tomany diseases, but its relationship with silicosis has not been reported. This research will carry out from cell, animal, the crowd with the methods and technics of cell biology, molecular biology and epigenetics. To establish a cells coculture model of silicosis in vitro, use confocal, electron microscopy, flow cytometry to verify the characteristics of circulating fibrocytes like stem cell. Use chip and co-immunoprecipitation experiments to explore epigenetic changes and compare the identical and difference with lung fibroblast cells, alveolar epithelial cells transdifferentiation. Establish silica dust aerosol dynamic inhalation animal model. Use fluorescence labeling, immunohistochemistry and flow cytometry to observe the morphological changes and the number of circulating fibrocytes in peripheral blood and lung tissue. And detect the the source and distribution of myofibroblasts in fiber tissue. Carry out case-control study, and detect the level of circulating fibrocytes and related factors in blood, sputum, and bronchoalveolar lavage fluid of workers exposed to dust and silicosis patients. And explore their value. It will provide new ideas and theory evidence for further reveale silicosis silicosis, find indicators of biological monitoring and early diagnosis, and seek for potential targets for intervention.

英文关键词： Circulating fibrocytes;stem cell;silicosis;pneumoconiosis;silica