机械拉伸对成纤维细胞生物学行为的影响及其机械生物学和神经炎症机理的实验研究

项目名称： 机械拉伸对成纤维细胞生物学行为的影响及其机械生物学和神经炎症机理的实验研究

项目编号： No.81201474

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 黄晨昱

作者单位： 煤炭总医院

项目金额： 23万元

中文摘要： 机械生物学信号转导和神经炎症与病理性瘢痕的发生发展密切相关。本研究在前期对瘢痕疙瘩标本进行cDNA基因微阵列分析，筛选体内瘢痕疙瘩在所处慢性机械刺激微环境下相对于自体正常皮肤机械生物学信号转导通路表达的变化。在此基础上，拟在体外构建成纤维细胞拉伸模型，观察拉伸刺激对成纤维细胞的形态影响及成纤维细胞增殖、分化、合成、运动等细胞功能的变化。并进一步在mRNA和蛋白质水平检测靶机械传导通路分子的表达。进而建立体外成纤维细胞与交感神经细胞的共培养体系，检测拉伸刺激下交感神经细胞来源的神经肽的mRNA和蛋白质表达及其对成纤维细胞的影响。同时观察交感神经细胞与成纤维细胞间的直接缝隙连接变化情况。通过从机械生物学膜途径、神经炎症旁分泌途径及可能的缝隙连接直接途径揭示体外拉伸刺激下成纤维细胞形态和功能改变的作用机理及三者之间的相互关系，阐明病理性瘢痕发生发展的机理，以期为病理性瘢痕的防治和干预提供靶分子。

中文关键词： 病理性瘢痕；细胞拉伸；力生物学；神经炎症；神经肽

英文摘要： Pathological scars are typical fibroproliferative skin disorders. Mechanobiology and neuroinflammation have increasingly been recognized showing close relationship to the development and progression of pathological scars. Purpose of this study is to explore the mechanisms of mechanotransduction, neuroinflammation, the potential direct gap-junction communication, and their potential communications related to formation of pathological scars.Based on the former trials of cDNA microarray analysis on in vivo keloid samples to screen out the potential mechanotransduction pathways, in this main study, the in vitro cellular stretching model will be set up to explore the effects of cellular stretch for dermal fibroblasts on their cellular behaviors of morphology and functions such as proliferation, differentiation, synthesis and migration. Furthermore, the expressions of the intracellular mechanotransduction pathway molecues will be examined at mRNA and protein levels through real-time RT-PCRA and ELISA methods, respectively. After that, the in vitro co-culture system of dermal fibroblasts and sympathetic nerve cells will be developed in vitro for the following celluar stretching. The sympathetic nerve cell-derived neuropeptides in this system and the potential direct gap junction between fibroblasts and sympathtic nerv

英文关键词： Pathological scar；cellular stretch；mechanobiology；neuroinflammation；neuropeptide