蛛网膜下腔出血（SAH）具有高致死、致残率，早期脑损伤是其重要的致病机制。最新的研究发现铁死亡（ferroptosis）即铁依赖的非凋亡性细胞死亡，在多种疾病的发生和发展中扮演着重要角色，但在SAH中未见报道。本课题组预实验发现SAH后早期神经元在电镜下呈现铁死亡的特异征象，而且铁死亡的抑制剂liproxtatin-1可明显改善SAH小鼠神经功能障碍，提示铁死亡可能在SAH后早期脑损伤中发挥重要作用。在前期研究基础上，我们推测SAH后铁死亡可能是铁调素/铁输出蛋白（Hepcidin/ferroportin)介导的铁超载引起，而我们预实验发现铁调素表达增加，而其上游的调控通路HDAC3/NOCR1表达下降。本课题将利用临床标本、Hepcidin-/-小鼠、原代神经元和PC12细胞，从多个层面明确铁死亡在SAH后早期脑损伤中的作用，并进一步阐明铁调素/铁输出蛋白对其的调控机制。

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality and morbidity. Early brain injury (EBI) is an important pathological process of SAH, and how to relieve EBI has become a research hotspot. The latest studies demonstrate that ferroptosis, a nonapoptotic and iron-dependent cell death, plays an important role in the pathogenesis of many diseases. However，its effect on SAH is unclear . Our recent preliminary study found that neurons showed some ferroptosis special signs in acute stage of SAH, and ferroptosis inhibitor, liproxstatin-1, could improve the neurological function in mice after SAH, indicating the important role of ferroptosis in EBI after SAH. On the findings of the latest researches and our preliminary experiment, we suppose that the neuronal ferroptosis following SAH is induced by the failure of cellular iron export regulated by Hepcidin/ferroportin. Moreover, our preliminary research found that the level of Hepcidin was increased and the expression of HDAC3/NOCR1, as an upstream regulatory signal pathway, was decreased. With the experimental techniques of transmission electron microscopy, flow cytometer, RNA interference, CRISPR/CAS9, 7.0T MRI, the current study was undertaken to investigated the role of neuronal ferroptosis in EBI after SAH, and to clarify the Hepcidin/ferroportin related regulation mechanisms in vivo and in vitro with clinical samples, Hepcidin-/- mice， primary neuron culture and PC12 cells. The result of this study would provide some preclinical basis for the specific and effective treatment of EBI after SAH.