eCBs-Wnt-OPCs体系调控胶质瘢痕功能在脊髓损伤功能恢复中的作用机制研究

The role of glial scar in functional recovery of traumatic spinal cord injury (SCI) has been recognized in recent years. It is also a regulation target for glial scar function. It is also becoming a therapeutic target for axonal regeneration after SCI. Oligodendrocyte precursor cells (OPCs, also known as NG2 positive cells) differentiate into astrocytes oligodendrocytecells rapidly after spinal cord injury. Oligodendrocyte precursor cells is an important CNS cells to restore nerve function ,because of the characteristic ability of differentiation in mature mammals, whether the role of oligodendrocyte precursor cells in forming glial scar is still not clear. Our colleagues and our research results indicate that the endocannabinoid system has therapeutic effects on spinal cord ischemic injury tolerance and traumatic spinal cord on locomotors recovery. At the same time, cannabinoid receptor 1 (CB1R) is an important regulatory receptor for the differentiation of OPCs. According to the domestic and foreign research and our previous research on spinal cord injury , our studies were designed to prove the key role of OPCs in glial scar formation with NG2-CreER BAC in transgenic mice, and the mechanism is a CB1R dependent feature with specific CB1R conditional knockout mice. Behaviourology, genetics chemistry, cytology ,animal traumatic spinal cord injury model was used to clarify the role of OPCs in formation of glial scar ,and CB1R agonists, through activation of the Wnt pathway, play a key role in the regulation of OPCs differentiation in glial scar formation. So the regulation of glial scar after spinal cord injury maybe a new way to promote axonal reconstruction after spinal cord injury..

近年来，胶质瘢痕在创伤性脊髓损伤功能恢复中的重要作用有了新的认识，对胶质疤痕形成进行分时程调控，也成为脊髓损伤后轴突再生治疗的新观点。少突胶质细胞前体细胞（OPCs）在脊髓损伤后快速激活分化，在中枢神经系统神经功能恢复中发挥重要作用，但OPCs如何参与胶质瘢痕形成尚不清楚。国内外同行与我们的研究结果均表明，CB1R及其配体在脊髓损伤功能恢复中发挥着关键作用，可调节OPCs诱导及分化。为此本课题在国内外研究及课题组前期工作基础上，拟通过NG2-CreER BAC转基因小鼠及特异性条件性CB1R敲除小鼠证明：损伤发生后CB1R调控OPCs分化，并通过控制Wnt通路诱导胶质疤痕形成的关键机制；综合运用神经行为学、化学遗传学、脊髓创伤模型、细胞学实验等手段，阐明损伤发生的不同阶段调控CB1R-OPCs-Wnt通路对胶质疤痕形成及轴突重建的影响，为脊髓损伤的治疗及功能恢复奠定理论基础。

近年来，胶质瘢痕在创伤性脊髓损伤功能恢复中的重要作用有了新的认识，对胶质疤痕形成进行分时程调控，也成为脊髓损伤后轴突再生治疗的新观点。少突胶质细胞前体细胞（OPCs）在脊髓损伤后快速激活分化，在中枢神经系统神经功能恢复中发挥重要作用，但OPCs如何参与髓鞘再生运动功能恢复及胶质瘢痕形成尚不清楚。国内外同行与我们的研究结果均表明，CB1R及其配体在脊髓损伤功能恢复中发挥着关键作用，可调节OPCs诱导及分化。为此本课题在国内外研究及课题组前期工作基础上，首先发现在脊髓损伤后CB1R激动剂ACEA可以促进OPC分化形成髓鞘并减少损伤部位的胶质瘢痕，改善小鼠运动功能。接下来我们通过体内实验与体外实验少突胶质细胞原代培养相结合，证明了wnt通路可能是ACEA通过IL-33表达进行调控，作为IL-33调控的下游机制，且进一步证明IL-33可以促进脊髓损伤后的髓鞘恢复并改善运动功能。阐明损伤发生的不同阶段调控CB1R-OPCs-Wnt通路对胶质疤痕形成及轴突重建的影响，为脊髓损伤的治疗及功能恢复奠定理论基础。

内容获取失败，请点击重试