Postoperative cognitive dysfunction (POCD) is a common complication induced by anesthesia or surgery, which affects the concentration, cognition and memory of patients. Sevoflurane, a clinical anesthetic, could stimulate neuro-inflammation and lead to POCD. Recent studies found that specificity protein 1 (SP1) participates in the development of neurological diseases. Our study aims to elucidate the role of SP1 in sevoflurane-induced POCD pathogenesis. We anesthetized Sprague–Dawley rats and treated the primary hippocampal neurons with sevoflurane to construct the in vivo and in vitro POCD models. Besides, the expression and regulatory mechanism of SP1 in the pathogenesis of POCD were explored. According to the results, sevoflurane anesthesia impaired the cognitive functions of rat, significantly elevated SP1 expression and inactivated the cholinergic anti-inflammatory pathway (CAP) both in vivo and in vitro. Moreover, the sevoflurane-treated rats and neurons also exhibited obvious inflammatory responses and enhanced apoptosis. Loss-of-function assay indicated that SP1 knockdown rescued the deactivation of CAP and alleviated the sevoflurane-induced neuro-inflammation and apoptosis in rat hippocampus. Generally, our study documented that the sevoflurane-induced SP1 up-regulation affected the activation of CAP, leading to the aggravated neuro-inflammation and apoptosis. This may provide a novel sight for POCD therapy.

术后认知功能障碍（POCD）是麻醉或手术诱发的常见并发症，影响患者的注意力、认知和记忆力。七氟醚是一种临床麻醉剂，可刺激神经炎症并导致 POCD。最近的研究发现特异性蛋白1（SP1）参与了神经系统疾病的发展。我们的研究旨在阐明 SP1 在七氟醚诱导的 POCD 发病机制中的作用。我们麻醉 Sprague-Dawley 大鼠并用七氟醚处理初级海马神经元以构建体内和体外 POCD 模型。此外，探讨了SP1在POCD发病机制中的表达及调控机制。结果表明，七氟醚麻醉会损害大鼠的认知功能，在体内和体外均显着提高 SP1 表达并使胆碱能抗炎通路 (CAP) 失活。此外，七氟醚处理的大鼠和神经元也表现出明显的炎症反应和增强的细胞凋亡。功能丧失测定表明，SP1 敲低挽救了 CAP 的失活并减轻了七氟醚诱导的大鼠海马神经炎症和细胞凋亡。一般来说，我们的研究表明，七氟醚诱​​导的 SP1 上调影响 CAP 的激活，导致神经炎症和细胞凋亡加重。这可能为 POCD 治疗提供新的视角。功能丧失测定表明，SP1 敲低挽救了 CAP 的失活并减轻了七氟醚诱导的大鼠海马神经炎症和细胞凋亡。一般来说，我们的研究表明，七氟醚诱​​导的 SP1 上调影响 CAP 的激活，导致神经炎症和细胞凋亡加重。这可能为 POCD 治疗提供新的视角。功能丧失测定表明，SP1 敲低挽救了 CAP 的失活并减轻了七氟醚诱导的大鼠海马神经炎症和细胞凋亡。一般来说，我们的研究表明，七氟醚诱​​导的 SP1 上调影响 CAP 的激活，导致神经炎症和细胞凋亡加重。这可能为 POCD 治疗提供新的视角。