脑出血(Intracerebral hemorrhage, ICH)发生发展过程中，占位效应不仅影响脑组织的物理结构甚至导致脑疝，而且与ICH后的神经损伤、预后水平和死亡率具有十分紧密的联系。然而，占位效应导致神经损伤的途径并不十分清楚。课题组前期发现ICH急性期内血肿及水肿产生的占位效应所诱导的静水压导致周围脑组织产生损伤。本项目拟在此基础上，建立体内体外静水压加载细胞或动物模型，探讨力学通道蛋白Piezo在ICH急性期内静水压导致神经损伤过程中的时间量效关系；同时，利用化学阻断剂/激动剂、基因沉默技术和Piezo基因敲除老鼠，研究JNK/Akt/NLRP3信号通路在静水压导致神经损伤过程中的作用，明确力学效应直接发挥损伤作用的途径。最终，揭示ICH后急性期Piezo介导的神经损伤作用及机制，为ICH急性期占位效应导致神经损伤的防治提供新的理论依据、治疗靶点和策略。

In the onset and development of intracerebral hemorrhage (ICH), mass effect not only changes the brain’s architecture and even leads to life-threatening brain herniation, but also has a close relationship with neural injuries, poor outcomes and high mortality. However, the effect of mass effect on neural injuries and the related pathways were not clear. We previously discovered that mass effect-induced hydrostatic pressure from the hematoma and brain edema gave rise to brain injuries directly in the acute phase after ICH. In light of this, we plan to establish the in vitro and vivo controllable hydrostatic pressure-loaded cell or rat model, and investigate the time dose-effect relationship of expression of Piezo induced by the hydrostatic pressure in the acute phase after ICH. Moreover, with the usage of agonist/antagonist, the method of gene silence and knock-out rat, we try to research the regulating effect of JNK/Akt/NLRP3 signal pathway on the neural injuries induced by hydrostatic pressure. Finally, we aim to reveal the signal pathways of neural injuries mediated by Piezo, and provide new therapeutic targets and strategies for the neural injuries in the acute phase after ICH.