蛛网膜下腔出血（SAH）是临床常见的危急重症，神经元凋亡在SAH后的早期脑损伤（EBI）中起关键作用，其具体分子机制不详。我们的前期研究发现，去泛素化酶BRCA相关蛋白1（BAP1）在SAH患者急性期脑脊液中显著升高；细胞实验显示过表达BAP1显著促进神经元P53的表达及氧合血红蛋白诱导的细胞凋亡；生物信息学分析提示转录因子2（ATF2）可与BAP1启动子区结合，调控转录过程。因此我们提出假说：SAH后ATF2通过激活转录过程上调神经元中BAP1的表达，促进P53去泛素化，稳定P53蛋白，激活P53调控的凋亡信号，诱导神经元凋亡和EBI发生。本研究旨在从分子、细胞和模型动物水平，借助于多种分子和细胞生物学技术手段，探讨ATF2转录调控BAP1介导P53去泛素化参与SAH后EBI的作用及机制。研究结果不仅有助于完善SAH后EBI发生发展的分子机制，且有望为SAH的治疗提供新的药物干预靶点。

Subarachnoid hemorrhage (SAH) is one of the most common critical and severe diseases. Neuronal apoptosis plays a key role in early brain injury (EBI) following early stage of subarachnoid hemorrhage (SAH), but the specific molecular mechanism remains unclear. Our preliminary studies showed that the expression of deubiquitylase BRCA associated protein 1 (BAP1) was significantly up-regulated in the cerebrospinal fluid of SAH patient during the acute period. Overexpression of BAP1 significantly promoted P53 expression and Oxyhemoglobin-induced neuronal apoptosis. Bioinformatics analysis showed that activating transcription factor 2 (ATF2) could bind the promoter region of BAP1 and positively regulate the expression of BAP1. Therefore, we hypothesize that, ATF2 was activated and promotes BAP1 expression in neurons, which catalyzes P53 deubiquitination and stabilizes P53 protein, thereby activating downstream P53 mediated cell apoptosis signaling and finally induces neuronal apoptosis and EBI after SAH. The aim of this study is to investigate the role and mechanisms of BAP1 in neuron apoptosis at the molecular, cellular and model animal levels by multiple techniques of molecular and cell biology. The results not only help us to elucidate the intrinsic mechanism of P53 debiquitizated by BAP1 which was regulated by ATF2 in early brain injury after SAH, but also provide a new target for SAH therapy.