脑出血发病凶险，致死、致残率高。血肿周围大量免疫细胞及细胞因子相互作用形成炎性微环境，在脑出血的继发性损伤及修复过程中发挥关键作用。TREK-1是双孔钾通道家族成员，广泛参与了脑缺血、抑郁、疼痛等神经系统疾病的病理生理过程。激活TREK-1能减轻脑缺血后的炎性反应，促进神经功能恢复，但作用机制不明。申请者前期研究发现，TREK-1敲除促进了小鼠脑出血后小胶质细胞活化及促炎因子表达，提示其在脑出血后的炎症及免疫应答中发挥重要调控作用。据此，我们推测TREK-1通过调控脑出血炎性微环境，促进其从神经损害向神经保护表型转化，进而发挥脑保护作用。为验证以上假说，本项目拟采用TREK-1敲除鼠建立脑出血模型，结合膜片钳、免疫组化、分子生物学等方法，从分子、细胞、整体水平研究TREK-1在调控脑出血炎性微环境，减轻继发性脑损伤中的作用机制，为深入理解脑出血的损伤机制，探索新的治疗靶点提供理论依据。

Intracerebral hemorrhage (ICH) is characterized by high mortality and disability. After the ICH, a large number of immune cells and inflammatory factors interact to form an inflammatory microenvironment, playing a key role in the disease process. As a member of the two-pore potassium channel (K2P) family, TREK-1 is widely involved in the pathophysiological process of neurological diseases such as cerebral ischemia, depression and pain. After cerebral ischemia, TREK-1 activation can reduce inflammatory response and promote the recovery of neurological function, but the mechanism remains unclear. Our previous studies showed that knockout of TREK-1 promoted the activation of microglial and the expression of proinflammatory factors in mice with ICH, suggesting that TREK-1 may be involved in the inflammation and immune response. Thus, we propose that TREK-1 may exerts neuroprotective effects after the ICH by regulating the inflammatory microenvironment and promoting its transformation from a neurologically damaged phenotype to a neuroprotective phenotype. In this project, TREK-1 gene knockout mice will be used to establish the ICH model, and the role of TREK-1 in the regulation of inflammatory microenvironment will be studied at the molecular, cellular and whole levels using patch clamp, immunohistochemistry and molecular biology methods. This project will provide theoretical basis for further understanding the injury mechanism of ICH and exploring new therapeutic targets.