继发性脑损伤是脑出血（ICH）致死致残率居高不下的主要原因，但临床上干预手段缺乏。最新研究发现，节律基因在细胞应激反应调节中具有重要作用，但其在ICH继发性脑损伤中的作用尚未明确。课题组通过ICH患者脑组织标本检测及转基因动物的验证发现，ICH后节律基因Rev-Erbα下调可能是ICH继发性神经损伤加重的关键因素。进一步预实验提示Rev-Erbα可能通过抑制自噬关键转录因子TFEB的转录活性，维护自噬稳态。据此我们假设：ICH后Rev-Erbα功能下调，抑制TFEB转录活性的作用减弱，诱发神经细胞过度自噬而死亡，从而加重ICH继发性脑损伤。基于此，本课题拟采取“临床问题-基础研究-转化应用”的策略，借助多种基因模式动物和ICH模型动物，阐明ICH继发性脑损伤的关键病理机制，为临床有效干预提供新思路。

Secondary brain injury after ICH is the main cause of the high mortality and disability. However, there is lack of clinical intervention currently. Recent studies have found that the circadian gene played an important role in the regulation of cellular stress response, but its role in secondary brain injury after ICH is not yet clear. Through the detection of brain samples from ICH patients and the verification of transgenic animals, we found that the downregulation of circadian gene Rev-Erbα after ICH may be the key factor for the aggravation of secondary nerve injury of ICH. Further preliminary experiments suggested that Rev-Erbα might maintain autophagy homeostasis by inhibiting the transcriptional activity of the key autophagy transcription factor TFEB. Accordingly, we hypothesized that the downregulation of Rev-Erbα might induce excessive autophagy of nerve cells because the inhibition of TFEB transcriptional activity was weakened, thus aggravating the secondary brain injury after ICH. Based on this, we intend the research strategy of “clinical problems-basic research-translational application” here. With a variety of transgenic mice and ICH animal model, we will elucidate the key pathological mechanism of secondary brain injury after ICH and provide new thought for clinical effective intervention.