RIP1/RIP3/MLKL介导的细胞程序性坏死（Necroptosis）参与多种神经系统疾病的脑损伤过程，但该通路在蛛网膜下腔出血（SAH）脑损伤中作用尚不清楚。我们前期研究发现RIP1、RIP3、MLKL蛋白在SAH大鼠脑组织中被激活，采用Necrostatin-1抑制RIP1激酶活性可以明显减轻细胞坏死和炎症反应，并且促进功能恢复，提示RIP1激活在SAH脑损伤中发挥重要作用，但是RIP3和MLKL的作用还不清楚。因此，本课题拟通过血管内穿刺、血红蛋白诱导来建立SAH的体内、体外模型，并借助基因敲除和化学抑制手段分别对RIP3、MLKL在SAH脑损伤中作用进行研究，以进一步明确RIP1/RIP3/MLKL通路介导的程序性坏死在SAH中的激活情况及其与脑损伤的关系，为SAH治疗提供新的靶点。

RIP1/RIP3/MLKL-mediated necroptosis is involved in brain injuries caused by a variety of neurological diseases, but its role in subarachnoid hemorrhage (SAH) is still unknown. Our previous study found that RIP1, RIP3 and MLKL proteins were activated in brain tissue of SAH rats. Inhibition of RIP1 kinase activity with necrostatin-1 could significantly reduce necrosis and inflammation, and promote functional recovery, suggesting that RIP1 activation plays a crucial role in SAH-induced brain injury. However, the role of RIP3 and MLKL is unclear. Therefore, the present study intends to establish models of SAH in vivo and in vitro by endovascular perforation and hemoglobin induction, and then explores the effect of RIP3 and MLKL on brain injury following SAH by means of gene knockout and chemical inhibition, to further clarify the activation of RIP1/RIP3/MLKL-mediated necroptosis and its effects on brain injury, providing a new target for the treatment of SAH.