线粒体自噬调控神经元程序性坏死在蛛网膜下腔出血后早期脑损伤中的机制研究

蛛网膜下腔出血（SAH）是一种严重危害健康的脑血管疾病，它引发的早期脑损伤是其首要的致病机制，但目前仍缺乏有效的干预手段。我们的前期研究发现，自噬/线粒体自噬的激活能显著减轻SAH后早期神经元细胞死亡，从而发挥显著的神经保护作用，但其具体机制尚不明确。程序性坏死是SAH后早期脑损伤中神经元细胞死亡的重要方式，但目前尚未有研究报道SAH后线粒体自噬和其的联系。我们的最新研究发现，线粒体自噬能调控神经元细胞程序性坏死，激活/抑制线粒体自噬能显著削弱/加重SAH后早期神经元细胞坏死情况。因此我们将进一步深入研究线粒体自噬－程序性坏死调控信号通路，利用SAH动物和细胞模型，采用免疫印迹组化、RNA干扰、CRISPR/Cas9等技术，从体内、体外两个层面，阐明线粒体自噬调控SAH后早期神经元细胞程序性坏死的具体作用机制，为临床治疗SAH提供新思路和理论依据。

Subarachnoid hemorrhage(SAH) is a devastating disease with high mortality and significant morbidity among patients. Early brain injury (EBI) following SAH is considered as the primary cause of poor outcome after SAH and remains no effective therapy. Our previous studies have demonstrated that autophagy/mitophagy activation is neuroprotective against EBI after SAH, which is associated with the reduced neuronal cell death in the early stage of SAH. However, the exact molecular mechanism of that remains obscure. Necroptosis is a major component of neuronal cell death after SAH. However, there are not any research focused on the relationship between mitophagy and necroptosis. Our further research found that necroptosis was significantly regulated by autophagy in SAH rat model, and activating/inhibiting mitophagy could significantly reduce/increase necroptosis in the early stage of SAH. This study was undertaken to investigate the role and the mechanisms of mitophagy mediated necroptosis in EBI following SAH in both animal and cellular levels, and thus to provide a new target for SAH treatment.