蛛网膜下腔出血（SAH）后脑损伤严重影响患者预后，但目前对其病理分子机制认识甚微。我们前期研究发现SAH后脑内Toll样受体4（TLR4）及高迁移率族蛋白1（HMGB-1）表达增高，神经元中施加外源性重组HMGB-1可诱发炎性反应。结合国际最新研究，我们推测作为DNA结合蛋白的HMGB-1，是损伤相关分子模式（DAMP）的重要炎性介质，最初由血细胞裂解被动释放，通过TLR启动炎性反应，刺激神经细胞损伤后再次主动释放，呈"双相"效应，级联放大DAMP型炎性反应，即SAH后脑损伤的核心因素。本课题拟通过体内、体外实验，针对HMGB-1，运用特异性抑制剂、重组HMGB-1、RNA干扰及基因过表达技术，立足DAMP分子机制，探讨HMGB-1在SAH后脑损伤中的具体作用机制。通过此项研究，有助于深入理解SAH后DAMP型炎性反应与脑损伤的关系，为SAH后脑损伤的临床治疗提供新的靶点，并奠定理论基础。

The brain injury after subarachnoid hemorrhage(SAH) usually brings poor outcomes to the patients, while the mechanisms have not been well elucidated. We previously found an up-regulation of Toll-like receptor 4(TLR4) and high-mobility group box 1(HMGB-1) in the cerebral cortex after SAH. Moreover, we found that inflammatory response could be induced and amplified following recombinant HMGB-1(rHMGB-1) addition in cultured neurons. Based on the latest research in this field, we raised a hypothesis that HMGB-1, a DNA-binding protein, was a prototypical member of damage-associated molecular pattern(DAMP) family and could be passively released from the hemotocyte lysis to initiate the inflammation through TLR. The inflammatory mediators then acted on the neuronal cells to make them actively release HMGB-1 continuously, manifesting as double phases. HMGB-1 might be able to induce and amplify sterile inflammation, and thus be the key factor of brain injury after SAH. In this study, we are planning to apply specific inhibitors, rHMGB-1, RNA interference and gene overexpression aiming at HMGB-1 to investigate the mechanisms of HMGB-1 in brain injury after SAH, which will be validated through DAMP-induced inflammation both in vivo and in vitro. From this research, we expect to better understand the relationship between DAMP-induced inflammation and brain injury, thereby providing a novel therapeutic target and establishing a rationale for brain injury after SAH.