Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Road, Hangzhou, Zhejiang Province 310003, China.
Department of Anesthesiology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, China.
Brain Res Bull. 2022 Jun 1;183:142-152. doi: 10.1016/j.brainresbull.2022.03.006. Epub 2022 Mar 11.
Sevoflurane, a commonly used inhaled anesthetic, causes endogenous apoptosis in fetal rats. Microglia polarization is associated with inflammation, and the IL-10/STAT3/SOCS3 pathway is involved in this process. Neuroglobin (Ngb) is a neuroprotective protein which exhibits an anti-inflammatory effect. The purpose of this study was to investigate whether neurotoxicity induced by sevoflurane exposure in prenatal rats correlates with neuroinflammation and microglia polarization and whether Ngb can moderate this response. We found that exposure to sevoflurane on the 20th day of gestation (G20) induced discernable inflammation in postnatal day 0 (P0) rats, promoted M1 polarization of microglia, and inhibited M2 polarization. Hemin-mediated Ngb elevation inhibited sevoflurane-induced neuroinflammation. Additionally, elevated Ngb inhibited M1 polarization and promoted M2 polarization of microglia. We also found that elevated Ngb could alleviate the effect of sevoflurane on the expression of Interleukin-10 (IL-10), phosphorylated-signal transduction and activators of transcription 3 (P-STAT3), and suppressor of cytokine signaling 3 (SOCS3). Furthermore, we found that elevated Ngb ameliorated the effects of sevoflurane on long-term exploratory behavior and learning and memory in the offspring. Our results show that Ngb alleviates the neurotoxicity of sevoflurane to fetal rats by inhibiting neuroinflammation and affecting microglial polarization, a process which may involve the IL-10/STAT3/SOCS3 pathway.
七氟醚是一种常用的吸入性麻醉剂，可导致胎鼠内源性细胞凋亡。小胶质细胞极化与炎症有关，IL-10/STAT3/SOCS3 通路参与这一过程。神经球蛋白（Ngb）是一种神经保护蛋白，具有抗炎作用。本研究旨在探讨胎鼠暴露于七氟醚是否与神经炎症和小胶质细胞极化有关，以及 Ngb 是否可以调节这种反应。我们发现，妊娠第 20 天（G20）暴露于七氟醚可诱导出生后第 0 天（P0）大鼠明显的炎症反应，促进小胶质细胞 M1 极化，并抑制 M2 极化。血红素介导的 Ngb 升高可抑制七氟醚诱导的神经炎症。此外，升高的 Ngb 抑制小胶质细胞 M1 极化并促进 M2 极化。我们还发现，升高的 Ngb 可以减轻七氟醚对白细胞介素-10（IL-10）、磷酸化信号转导和转录激活因子 3（P-STAT3）和细胞因子信号转导抑制因子 3（SOCS3）表达的影响。此外，我们发现升高的 Ngb 可改善七氟醚对后代长期探索行为和学习记忆的影响。我们的结果表明，Ngb 通过抑制神经炎症和影响小胶质细胞极化来减轻七氟醚对胎鼠的神经毒性，这一过程可能涉及 IL-10/STAT3/SOCS3 通路。
