The involvement of Dexmedetomidine (Dex) has been indicated in postoperative cognitive dysfunction (POCD), while the mechanism is not well characterized. This study estimated the mechanism of Dex in POCD. Rats were anesthetized with sevoflurane (SEV) to evoke POCD and then subjected to Morris water maze test to detect the cognitive and behavioral function. Then, the damage of hippocampus and cortex, and apoptosis and activity of neurons were examined. Microarray analysis was performed to screen out the differentially expressed microRNAs (miRs) in rats after Dex treatment. The cognitive and behavioral functions and neuronal activity of rats were detected after miR-129 antagomir injection. The target of miR-129 was predicted. The levels of TLR4 and NF-κB p65 in hippocampus and cortex were measured. Dex treatment alleviated SEV-induced behavior and cognitive impairments in rats, promoted neuronal activity and hindered neuronal apoptosis. After treatment with Dex, miR-129 expression was elevated in brain tissues, and the neuroprotection of Dex on POCD rats was partially annulled after injection of miR-129 antagomir. Furthermore, miR-129 targeted TLR4 and prevented the phosphorylation of NF-κB p65. In summary, Dex ameliorated SEV-induced POCD by elevating miR-129 and inhibiting TLR4 and NF-κB p65 phosphorylation. This study may shed new lights on POCD treatment.

右美托咪定 (Dex) 的参与已表明术后认知功能障碍 (POCD)，但其机制尚未得到很好的表征。本研究估计了 Dex 在 POCD 中的作用机制。大鼠用七氟醚（SEV）麻醉诱发POCD，然后进行Morris水迷宫试验以检测认知和行为功能。然后，检查海马和皮层的损伤，以及神经元的凋亡和活性。进行微阵列分析以筛选出 Dex 治疗后大鼠中差异表达的 microRNAs (miRs)。注射miR-129 antagomir后检测大鼠的认知行为功能和神经元活动。预测了 miR-129 的靶点。测量海马和皮层中 TLR4 和 NF-κB p65 的水平。Dex 治疗减轻了 SEV 诱导的大鼠行为和认知障碍，促进了神经元活动并阻碍了神经元凋亡。用 Dex 治疗后，脑组织中 miR-129 表达升高，注射 miR-129 antagomir 后，Dex 对 POCD 大鼠的神经保护作用部分消失。此外，miR-129 靶向 TLR4 并阻止 NF-κB p65 的磷酸化。总之，Dex 通过提高 miR-129 并抑制 TLR4 和 NF-κB p65 磷酸化来改善 SEV 诱导的 POCD。这项研究可能会为 POCD 治疗提供新的线索。miR-129 靶向 TLR4 并阻止 NF-κB p65 的磷酸化。总之，Dex 通过提高 miR-129 并抑制 TLR4 和 NF-κB p65 磷酸化来改善 SEV 诱导的 POCD。这项研究可能会为 POCD 治疗提供新的线索。miR-129 靶向 TLR4 并阻止 NF-κB p65 的磷酸化。总之，Dex 通过提高 miR-129 并抑制 TLR4 和 NF-κB p65 磷酸化来改善 SEV 诱导的 POCD。这项研究可能会为 POCD 治疗提供新的线索。