GIT1CC2结构域在保护脊髓缺血再灌注损伤（SCII）中的机制研究

脊髓缺血再灌注损伤(SCII)是脊柱外科的临床难题。目前的研究普遍认为：氧自由基介导的过氧化反应所产生的活性氧簇（ROS）以及由ROS激活的凋亡信号调节激酶（ASK1）是造成脊髓缺血再灌注损伤的关键。GIT1是保护脑和脊髓组织的重要蛋白质。我们最近的研究表明：GIT1蛋白参与了保护脊髓和神经细胞的功能（Zhou et al：BRB等）。本研究采用国内唯一具有的GIT1基因敲除型小鼠，建立经典的脊髓缺血再灌注动物模型，运用免疫杂交，免疫共沉淀，免疫组化和免疫荧光等方法探讨ASK1通过磷酸化GIT1CC2结构域中的丝氨酸，使磷酸化后的GIT1CC2结构域和ASK1的CC结构域相互结合，从而抑制ASK1酶的活性，减轻脊髓组织在缺血再灌注中的损伤。阐明GIT1在脊髓缺血再灌注中的作用，不仅掌握脊髓缺血再灌注损伤的病理学机制，同时也为临床更有效地预防和治疗脊髓缺血再灌注损伤提供坚实的理论依据。

Spinal cord reperfusion injury (SCII) is a serious clinical problem in spinal department. Oxygen free radical mediated peroxidation and apoptosis signal-regulating kinase 1(ASK1) play an important role in SCII. G-protein coupled receptor kinase-interacting protein 1 (GIT1) is an important protein in protecting the brain and spinal cord tissues. We proved that GIT1 play a role in protecting spinal cord and neurons(Zhou W et al: 2013，Brain Res Bull；2014，Neurochem Res Bull). We will explore the function of GIT1 on SCII by immunoblotting, immunoprecipitation, immunofluorescence and luciferase report gene assay in GIT1 wild type (GIT1WT) and GIT1 knock out (GIT1KO) mice. ASK1 phosphorylates the serine in CC2 domain of GIT1 and then lead to the CC domain of ASK1 interact with CC2 domain of GIT1. This interaction will inhibit the ASK1 activation. To explore the function of GIT1 in spinal cord reperfusion injury, not only can understand the mechanism of spinal cord reperfusion injury, but also can prevent and treat the spinal cord reperfusion injury.