Department of Anesthesiology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, China.
J Cell Mol Med. 2021 Apr;25(7):3449-3459. doi: 10.1111/jcmm.16426. Epub 2021 Mar 3.
Tumour necrosis factor-α (TNF-α), a crucial cytokine, has various homeostatic and pathogenic bioactivities. The aim of this study was to assess the neuroprotective effect of ketamine against TNF-α-induced motor dysfunction and neuronal necroptosis in male C57BL/6J mice in vivo and HT-22 cell lines in vitro. The behavioural testing results of the present study indicate that ketamine ameliorated TNF-α-induced neurological dysfunction. Moreover, immunohistochemical staining results showed that TNF-α-induced brain dysfunction was caused by necroptosis and microglial activation, which could be attenuated by ketamine pre-treatment inhibiting reactive oxygen species production and mixed lineage kinase domain-like phosphorylation in hippocampal neurons. Therefore, we concluded that ketamine may have neuroprotective effects as a potent inhibitor of necroptosis, which provides a new theoretical and experimental basis for the application of ketamine in TNF-α-induced necroptosis-associated diseases.
肿瘤坏死因子-α（TNF-α）是一种重要的细胞因子，具有多种体内平衡和致病的生物活性。本研究旨在评估氯胺酮对雄性 C57BL/6J 小鼠体内 TNF-α 诱导的运动功能障碍和神经元坏死性凋亡以及 HT-22 细胞系体外的神经保护作用。本研究的行为测试结果表明，氯胺酮改善了 TNF-α 诱导的神经功能障碍。此外，免疫组织化学染色结果表明，TNF-α 诱导的脑功能障碍是由坏死性凋亡和小胶质细胞激活引起的，氯胺酮预处理可以通过抑制海马神经元中活性氧的产生和混合谱系激酶结构域样磷酸化来减轻。因此，我们得出结论，氯胺酮可能具有神经保护作用，作为一种有效的坏死性凋亡抑制剂，为氯胺酮在 TNF-α 诱导的坏死性凋亡相关疾病中的应用提供了新的理论和实验基础。
