中文摘要
脊髓损伤后血管受损造成的局部微循环障碍是脊髓继发性损伤加剧的重要原因,促进血管新生对神经功能的恢复具有重要的意义。大量研究表明Notch在血管新生中扮演着不可或缺的角色,但其对脊髓损伤后血管新生的调控机制还不明确。本课题前期研究发现,补肾活血汤能够上调VEGF及Notch通路,因此,本课题组拟通过(1)采用临床样本、建立基因敲除和过表达模型小鼠以及脊髓前角运动神经元低氧模型来探讨脊髓损伤(SCI)后Notch对脊髓血管新生的调控作用以及对脊髓前角运动神经元的影响;(2)通过建立Allen’s打击模型以及脊髓前角运动神经元低氧模型探讨补肾活血汤调控Notch通路对血管新生以及对SCI的干预作用,为临床治疗脊髓损伤提供新的治疗靶点和理论支持。
英文摘要
The dysfunction of microcirculation caused by vessel destruction would aggravate the secondary injury after the spinal cord injury (SCI) and the improvement of local microcirculation by promoting angiogenesis is important for the repair process for neurons in spinal cord. Numorous studies have demonstrated that Notch signaling pathway plays a critical role in angiogenesis, but the regulation mechanisms of angiogenesis by Notch pathway after SCI is still obscure. Previously, we found that Bushen Huoxue decoction could upregulate the mRNA level of VEGF and Notch. Therefore, we proposed that (1) we would collect clinical samples, establish the mice model of conditional gene knockout/gain-of-function of Notch, and build the hypoxia model of spinal motor neurons (SMNs) to explore the mechanisms of Notch signaling pathway in regulating angiogenesis in spinal cord and in reparing the SMNs. (2) we would establish Allen’s model of rats and hypoxia model of SMNs to explore the mechanism of Bushen Huoxue Decoction in mediating angiogenesis via Notch pathway and its effects in treating spinal cord injury, finally providing novel therapeutic targets and theoretical support for clinical treatment of SCI.
