氯胺酮通常被用于镇静、止痛和麻醉。许多证据表明它具有免疫调节作用。通过α7nAChR介导的胆碱能抗炎途径是抗炎疗法的突出靶点。然而，氯胺酮是否通过激活α7nAChR抑制神经细胞中的炎症水平还不清楚。我们使用脂多糖(LPS)在体外建立PC12细胞神经炎症模型，并在LPS前30分钟将α7nAChR siRNA转染到PC12细胞中以抑制α7nAChR基因表达。PC12细胞被LPS刺激24小时，在添加GTS-21和氯胺酮后2小时检测指标。结果表明，LPS增加了PC12细胞凋亡比例，激活了TLR4 / MAPK / NF-κB信号通路，并增加了白介素-6(IL-6)，白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的表达。氯胺酮减少了PC12细胞早期和晚期凋亡的比例，抑制了P65进入核内，降低了TLR4 / MAPK / NF-κB的激活，并改善神经炎症。然而，氯胺酮对神经元凋亡和神经炎症的改善作用在α7nAChRi组中被抑制。这表明α7nAChR在氯胺酮的抗炎过程中起关键作用。低剂量的氯胺酮通过激活α7nAChR介导的胆碱能抗炎途径抑制TLR4 / MAPK / NF-κB，从而对神经元凋亡和神经炎症产生保护性作用。版权所有© 2023。Elsevier B.V.出版。

Ketamine is commonly used for sedation, analgesia and anesthetics. Much evidence has shown that it has an immune-regulatory effect. The cholinergic anti-inflammatory pathway mediated by α7nAChR is a prominent target of anti-inflammatory therapy. However, whether ketamine suppresses inflammatory levels in nerve cells by activating α7nAChR remains unknown. Lipopolysaccharide (LPS) was used to establish the neuroinflammation model in PC12 cells in vitro, and α7nAChR siRNA was transfected into PC12 cells 30 min before LPS to inhibit gene expression of α7nAChR. PC12 cells were stimulated with LPS for 24 h, and the indicators were detected at 2 h after GTS-21 and ketamine were added. The results showed that LPS increased the proportion of PC12 cells apoptosis, activated TLR4/MAPK/NF-κB signaling pathway, and increased the expression of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Ketamine reduced the ratio of early apoptosis and late apoptosis of PC12, inhibited the entry of P65 into the nucleus, decreased the activation of TLR4/MAPK/NF-κB and improved neuroinflammation. However, the ameliorating effects of ketamine on neuronal apoptosis and neuroinflammation were inhibited in the α7nAChRi group. This indicated that α7nAChR played a key role in the anti-inflammatory process of ketamine. Low-dose ketamine inhibited TLR4/MAPK/NF-κB by activating the α7nAChR-mediated cholinergic anti-inflammatory pathway, thereby producing the protective effect on neuronal apoptosis and neuroinflammation.Copyright © 2023. Published by Elsevier B.V.