Dexmedetomidine (Dex) may exert neuroprotective effects by attenuating inflammatory responses. However, whether Dex specifically improves postoperative cognitive dysfunction (POCD) by inhibiting microglial inflammation through what pathway remains unclear. In this study, the POCD model was constructed by performing open surgery after 3 h of continuous inhalation of 3% sevoflurane to rats, which were intraperitoneally injected with 25 μg/kg Dex .5 h before anaesthesia. The results displayed that Dex intervention decreased rat escape latency, maintained swimming speed and increased the number of times rats crossed the platform and the time spent in the target quadrant. Furthermore, the rat neuronal injury was restored, alleviated POCD modelling-induced rat hippocampal microglial activation and inhibited microglial M1 type polarization. Besides, we administered Dex injection and/or CCAAT/enhancer-binding protein beta (CEBPB) knockdown on the basis of sevoflurane exposure and open surgery and found that CEBPB was knocked down, resulting in the inability of Dex to function, which confirmed CEBPB as a target for Dex treatment. To sum up, Dex improved POCD by considering CEBPB as a drug target to activate the c-Jun N-terminal kinase (JNK)/p-38 signaling pathway, inhibiting microglial M1 polarization-mediated inflammation in the central nervous system.

中文翻译：

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右美托咪定通过抑制 CCAAT/增强子结合蛋白 β 来减轻七氟烷麻醉下接受开放手术的大鼠海马神经元损失和认知能力下降

右美托咪定 (Dex) 可能通过减弱炎症反应发挥神经保护作用。然而，Dex是否通过什么途径抑制小胶质细胞炎症来特异性改善术后认知功能障碍（POCD）仍不清楚。本研究通过开腹手术，给大鼠连续吸入3%七氟醚3 h，麻醉前0.5 h腹腔注射25 μg/kg Dex，构建POCD模型。结果显示，Dex干预减少了大鼠的逃避潜伏期，维持了游泳速度，并增加了大鼠穿过平台的次数和在目标象限中停留的时间。此外，大鼠神经元损伤得以恢复，减轻了POCD模型诱导的大鼠海马小胶质细胞活化并抑制了小胶质细胞M1型极化。此外，我们在七氟烷暴露和开放手术的基础上进行了Dex注射和/或CCAAT/增强子结合蛋白β（CEBPB）敲低，发现CEBPB被敲低，导致Dex无法发挥作用，这证实CEBPB是Dex 治疗的目标。综上所述，Dex通过将CEBPB作为药物靶点激活c-Jun N末端激酶（JNK）/p-38信号通路，抑制中枢神经系统小胶质细胞M1极化介导的炎症，从而改善POCD。