CyPA/CD147信号通路在蛛网膜下腔出血后早期脑损伤中的作用机制研究

The pathogenesis of early brain injury (EBI) in subarachnoid hemorrhage (SAH) is remains uncertain, in which inflammation and apoptosis effect significantly.Cyclophilin A (CyPA)/CD147 signal pathway was involved in inflammatory reaction pathological process of many diseases. Our preliminary experimental results show that CyPA and CD147 were probably involved in the pathological process of EBI after SAH. To this end, we propose the hypothesis: The interaction of extracellular cyclophilin A with its membrance receptor activate neurons apoptotic pathway,which was invoved in the pathological process of SAH-induced EBI. To test this hypothesis, first of all,we apply rats SAH model in vivo and hemoglobin treated neuron-culture SAH model in vitro,and we interfere the interaction of CyPA and CD147 by recombinant human CyPA9 (rh CyPA), siRNA and monoclonal antibody of CD147, after verifying the effect of interference，then we observe brain injury in vivo and neurons injury in vitro to clear the role of CyPA/CD147 in SAH-induced EBI. Secondly, By western blot, immunofluorescence staining, and EMSA technology,we observe the expression or activation of key factors in the signal path,to analyze the potential molecular mechanisms accounting for CyPA/CD147 activating neuron apoptotic pathway invoved in SAH-induced EBI in vitro and in vivo. This study from multi-level of molecules, cells, tissues and animals which has important significance to clarify CyPA/CD147 signal pathway in SAH-induced EBI and will provide us new ideas and theoretical basis to improve the prognosis of SAH patients.

炎症反应和细胞凋亡在蛛网膜下腔出血（SAH）后的早期脑损伤（EBI）中发挥重要作用，Cyclophilin A (CyPA)/CD147信号通路参与许多疾病炎性反应的病理过程，因而CyPA、CD147可能参与SAH后EBI的病理过程。为此，我们提出假说：CyPA与受体CD147结合，激活神经元凋亡信号通路，导致EBI发生。为了验证该假说，我们使用大鼠SAH模型及体外血红蛋白处理神经元培养SAH模型，应用人重组CyPA、siRNA技术和CD147单克隆抗体等干预CyPA/CD147相互作用，体内观察脑损伤、体外观察神经元损伤情况；另一方面, 利用western blot、免疫荧光染色等手段, 观察信号通路关键因子的表达和激活情况，在体内外分析探讨CyPA/CD147通过神经元凋亡途径在SAH后EBI中可能的分子作用机制，为改善SAH预后提供新思路和理论依据。