复合自发电导管激活PI3K-AKT-eNOS通路介导周围神经血管化促进再生的机制研究

周围神经缺损是临床治疗难点。目前临床采用的神经导管仅能作为机械性通道，不能促进神经血管化而无法修复长段缺损。电刺激能加速神经血管化，因此研究能持续放电促进神经再生的支架具有突破意义。本项目前期通过一体化成型方法制作导电纳米支架氧化石墨烯（GO）/聚己内酯(PCL)能激活AKT-eNOS-VEGFR2通路促进神经血管化，但需外加电刺激，有局限性。压电材料聚偏氟乙烯三氟乙烯(PVDF-TrEF)能利用微小形变将机械能转换为电能。因此，本课题利用压电材料构建复合压电PVDF-TrEF/GO/PCL纳米支架，预实验证实其能自发电，并激活内皮细胞中对组织血管化起重要作用的PI3K及VEGFR2分子。下一步拟阐明其对内皮细胞及神经细胞的影响，通过分析PI3K、AKT、eNOs及VEGF表达探讨其对神经血管化的作用机制。建立大鼠神经缺损模型，探讨其促进再生的体内作用及机制，为修复长段神经缺损提供新选择。

Peripheral nerve defect is difficult to deal with in clinical medical treatment. At present, the nerve conduit widely used in clinic but it could only provide as a mechanical channel. It couldn’t promote neurovascularization and peripheral nerve regeneration.So it can not repair long distance defects in nerve injury. Electrical stimulation could accelerate neurovascularization, so it is of breakthrough significance to study the scaffold which could promote nerve regeneration by supply continuous discharge. In the early stage of this project, graphene oxide (GO)/ polycaprolactone (PCL) prepared by integrated molding method could activate the AKT-eNOS-VEGFR2 pathway to promote neurovascularization and nerve regeneration, but it needs external electrical stimulation, which has some shotcoming. The piezoelectric material Poly (vinylidene fluoride) trifluoroethylene (PVDF-TrEF) could convert mechanical energy into electrical energy by small deformation. Therefore, we would use piezoelectric materials to construct composite piezoelectric PVDF-TrEF/GO/PCL nanoscaffolds in this study, which were demonstrated that could generate electricity and activate PI3K and VEGFR2 molecules that play an important role in tissue vascularization in endothelial cells. The next step is to clarify its effects on endothelial cells and nerve cells, and to explore its mechanism on neurovascularization by analyzing the expression of PI3K, AKT, eNOs and VEGF. Then to establish a rat model of nerve defect and to explore its effect and mechanism of promoting regeneration in vivo, so as to provide a new way for repairing long distance nerve defect.