Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA; Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, China.
Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA; Department of Anesthesiology and State Key Laboratory of Oncology in South China and Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, China.
Brain Behav Immun. 2017 Mar;61:365-374. doi: 10.1016/j.bbi.2017.01.005. Epub 2017 Jan 10.
Postoperative cognitive dysfunction worsens patient outcome after surgery. Neuroinflammation is a critical neuropathological process for it. We determined the role of P2X7 receptors, proteins that participate in inflammatory response, in the neuroinflammation induction after surgery, and whether the choice of volatile anesthetics affects its occurrence. Eight-week old C57BL/6J or P2X7 receptor knockout male mice were subjected to right carotid arterial exposure under anesthesia with 1.8% isoflurane, 2.5% sevoflurane or 10% desflurane. They were tested by Barnes maze and fear conditioning from 2weeks after the surgery. Hippocampus was harvested 6h, 24h and 7days after the surgery for immunohistochemical staining and Western blotting. Mice with surgery under anesthesia with isoflurane, sevoflurane or desflurane took longer than control mice to identify the target box 1 or 8days after the training sessions in Barnes maze. Mice anesthetized by isoflurane or sevoflurane, but not by desflurane, had less freezing behavior than control mice in fear conditioning test. Mice with surgery and anesthesia had increased ionized calcium binding adapter molecule 1 and interleukin 1β in the hippocampus but this increase was smaller in mice anesthetized with desflurane than mice anesthetized with isoflurane. Mice with surgery had increased P2X7 receptors and its downstream molecule caspase 1. Inhibition or knockout of P2X7 receptors attenuated surgery and anesthesia-induced neuroinflammation and cognitive impairment. We conclude that surgery under desflurane anesthesia may have reduced neuroinflammation and cognitive impairment compared with surgery under isoflurane anesthesia. P2X7 receptors may mediate the neuroinflammation and cognitive impairment after surgery.
术后认知功能障碍会使患者术后的预后恶化。神经炎症是其关键的病理生理过程。我们确定了 P2X7 受体（参与炎症反应的蛋白）在手术后神经炎症诱导中的作用，以及挥发性麻醉剂的选择是否会影响其发生。将 8 周龄的 C57BL/6J 或 P2X7 受体敲除雄性小鼠在 1.8%异氟烷、2.5%七氟烷或 10%地氟烷麻醉下进行右侧颈动脉暴露。手术后 2 周，通过 Barnes 迷宫和恐惧条件反射测试对它们进行测试。手术后 6h、24h 和 7d 采集海马组织，进行免疫组织化学染色和 Western blot 分析。与对照组相比，在 Barnes 迷宫中，接受异氟烷、七氟烷或地氟烷麻醉的手术小鼠在训练后 1 或 8d 找到目标箱的时间更长。与对照组相比，在恐惧条件反射测试中，接受异氟烷或七氟烷麻醉但不接受地氟烷麻醉的小鼠的冻结行为减少。与接受异氟烷麻醉的小鼠相比，接受地氟烷麻醉的手术小鼠海马中离子钙结合接头分子 1 和白细胞介素 1β增加，但增加幅度较小。手术和麻醉的小鼠 P2X7 受体及其下游分子半胱氨酸蛋白酶 1 增加。P2X7 受体的抑制或敲除减轻了手术和麻醉引起的神经炎症和认知障碍。我们得出结论，与异氟烷麻醉下的手术相比，地氟烷麻醉下的手术可能会减少神经炎症和认知障碍。P2X7 受体可能介导手术后的神经炎症和认知障碍。
