围术期睡眠剥夺是一个普遍存在的问题，与术后慢性疼痛（CPSP）的发生具有强相关性，严重影响患者术后恢复与生活质量。我们的前期研究和现有文献提示，血脊髓屏障完整性破坏诱发小胶质细胞活化介导的神经炎症反应参与CPSP的发生。围术期睡眠剥夺通过Quaking调节脊髓微血管内皮细胞HECW2可变剪接，使其线性RNA与环状RNA产物失衡，介导内皮细胞间质化（EndoMT），手术创伤进一步加重该表型转变。在EndoMT进程中，Dab1信号被抑制，通过血管-神经通信，激活小胶质细胞触发神经炎症反应，并下调GABA能抑制性神经元功能，导致CPSP的发生。本项目分别在睡眠剥夺致术后慢性疼痛的大鼠模型和分离培养的脊髓微血管内皮细胞模型上，探讨Quaking调节HECW2可变剪接对EndoMT的调控及内皮细胞Dab1信号对血管-神经通信的调节，研究睡眠剥夺致CPSP的机制，为临床防治CPSP提供理论和实践基础。

Perioperative sleep deprivation is a clinically significant problem for many patients undergoing surgery, and has a strong correlation with chronic postsurgical pain (CPSP), which seriously affects the postoperative recovery and the quality of patients’ life. Our preliminary studies and the available literatures suggested that the impairment of blood spinal cord barrier (BSCB) integrity induces spinal microglia activation, which mediates neuroinflammation, contributes to the pathogenesis of CPSP. Perioperative sleep deprivation regulates the alternative splicing of HECW2 via Quaking in spinal cord microvascular endothelial cells, causes the imbalance of linear RNA and circular RNA levels, and induces the spinal cord microvascular Endothelial to mesenchymal transition (EndoMT). Surgical stress further aggravates EndoMT causing the damage of BSCB. During EndoMT, the inhibited Dab1 signal in endothelial cells mediates peripheral immunocytes migration and infiltration, triggers the activation of spinal microglia-mediated neuroinflammation, and downregulates the function of GABAergic inhibitory neurons, via vessel-neuro-communication, resulting in the development of CPSP. This study intends to investigate the regulation of EndoMT via Quaking-mediated HECW2 alternative splicing, and the regulation of vessel-neuro-communication via Dab1 signal, in a rat model of sleep deprivation-induced CPSP in vivo and in primary cultured spinal cord microvascular endothelial cells in vitro. This study will provide the specific mechanism of CPSP, and provide a new theoretical and practical basis for clinical prevention and treatment of CPSP induced by sleep deprivation.