Tnc在周围神经损伤再生中的作用及其分子机制研究

项目名称： Tnc在周围神经损伤再生中的作用及其分子机制研究

项目编号： No.81200932

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 顾芸

作者单位： 南通大学

项目金额： 23万元

中文摘要： 周围神经损伤及再生过程中施万细胞的增殖迁移以及促轴突生长的相关调节机制仍不完全清楚。前期的研究结果表明细胞外基质糖蛋白 Tnc (tenascin C) 在神经损伤与再生过程起着重要调控作用。基于人工神经网络分析结果，本研究拟通过体内外实验进一步论证Tnc作为成纤维细胞产生的损伤信号分子，以旁分泌的方式促施万细胞的增殖迁移及成髓鞘。利用Tnc重组蛋白及其下游的信号通路的抑制剂检测其对施万细胞的迁移、成髓鞘的影响。构建含有Tnc重组蛋白缓释的组织工程神经移植物修复大鼠坐骨神经缺损，或通过siRNA慢病毒载体转染实验动物，分别从功能学及形态学等方面评价Tnc对神经横断伤修复的作用。Tnc的研究具有重要的理论意义和潜在的临床价值，将为探索 Tnc复杂多样功能的分子机制和新型组织工程神经的研究提供重要线索。

中文关键词： 细胞外基质糖蛋白 TNC ( tenascin C )；周围神经再生；成纤维细胞；施万细胞；组织工程神经

英文摘要： The molecular mechanisms that are responsible for the proliferation, migration, and axon growth-promoting effects of Schwann cells during peripheral nerve injury and regeneration are still unclear. Our preliminary experiments, especially the analysis data of artificial neural network, suggested that the tenascin C (Tnc), an extracellular matrix glycoprotein, played a core role in the process of nerve injury and regeneration. Based on this, the present study aims to show that Tnc, as fibroblasts- produced damage signal molecule, could promote the proliferation, migration and myelination of Schwann cells in a paracrine manner by in vivo and in vitro experiments. Our plans are (1) to detect the migration and myelination of Schwann cells by using the recombinant Tnc protein and the inhitotors of its downstream signaling pathway; (2) to construct tissue engineered nerve grafts that contained the sustained released recombinant Tnc protein, or to perform the experiment of siRNA lentiviral vector transfection into the injured animal for repair of rat sciatic nerve defect, and further to evaluate the repair ourcome of Tnc for nerve transection injuries by the aid of functional and morphological methods. It is expected that our study regarding Tnc functions has the important theoretical significance and potential clinical

英文关键词： extracellular matrix glycoprotein TNC(tenascin C)；peripheral nerve regeneration；fibroblast；Schwann cell；tissue engineering nerve