Microglia-mediated neuroinflammation is associated with epilepsy. Switching microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype represents a novel therapeutic strategy for mitigating epileptogenesis. We previously found that dynorphins protected against epilepsy via activation of kappa opioid receptor (KOR). Here, this study aims to investigate the role and the mechanism of dynorphin in regulating microglial polarization. A pilocarpine-induced rat model of epilepsy was established and lipopolysaccharide (LPS)-activated BV-2 microglial cells were used as an inflammatory model to explore the mechanism of dynorphin regulating microglial polarization. Overexpression of the dynorphin precursor protein prodynorphin (PDYN) alleviated the pilocarpine-induced neuronal apoptosis, promoted microglial polarization to the M2 phenotype, and inhibited pilocarpine-induced Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway in the hippocampi of epileptic rats. Dynorphin activation of KOR promoted microglial M2 polarization via inhibiting TLR4/NF-κB pathway in LPS-stimulated BV-2 microglial cells. Moreover, dynorphin/KOR regulated microglial M2 polarization inhibited apoptosis of the primary mouse hippocampal neurons. In conclusion, dynorphin activation of KOR promotes microglia polarization toward M2 phenotype via inhibiting TLR4/NF-κB pathway.

中文翻译：

---

强啡肽激活κ阿片受体促进小胶质细胞通过 TLR4/NF-κB 通路向 M2 表型极化。

小胶质细胞介导的神经炎症与癫痫有关。将小胶质细胞极化从促炎 M1 表型转换为抗炎 M2 表型代表了一种减轻癫痫发生的新治疗策略。我们之前发现强啡肽通过激活 kappa 阿片受体 (KOR) 来预防癫痫。在这里，本研究旨在探讨强啡肽在调节小胶质细胞极化中的作用和机制。建立毛果芸香碱致癫痫大鼠模型，以脂多糖（LPS）激活的BV-2小胶质细胞为炎症模型，探讨强啡肽调控小胶质细胞极化的机制。强啡肽前体蛋白强啡肽原 (PDYN) 的过表达减轻了毛果芸香碱诱导的神经元凋亡，促进小胶质细胞向 M2 表型极化，并抑制癫痫大鼠海马中毛果芸香碱诱导的 Toll 样受体 4 (TLR4)/核因子-κB (NF-κB) 通路。KOR 的强啡肽激活通过抑制 LPS 刺激的 BV-2 小胶质细胞中的 TLR4/NF-κB 通路促进小胶质细胞 M2 极化。此外，强啡肽/KOR 调节的小胶质细胞 M2 极化抑制了原代小鼠海马神经元的凋亡。总之，强啡肽激活 KOR 通过抑制 TLR4/NF-κB 通路促进小胶质细胞向 M2 表型极化。KOR 的强啡肽激活通过抑制 LPS 刺激的 BV-2 小胶质细胞中的 TLR4/NF-κB 通路促进小胶质细胞 M2 极化。此外，强啡肽/KOR 调节的小胶质细胞 M2 极化抑制了原代小鼠海马神经元的凋亡。总之，强啡肽激活 KOR 通过抑制 TLR4/NF-κB 通路促进小胶质细胞向 M2 表型极化。KOR 的强啡肽激活通过抑制 LPS 刺激的 BV-2 小胶质细胞中的 TLR4/NF-κB 通路促进小胶质细胞 M2 极化。此外，强啡肽/KOR 调节的小胶质细胞 M2 极化抑制了原代小鼠海马神经元的凋亡。总之，强啡肽激活 KOR 通过抑制 TLR4/NF-κB 通路促进小胶质细胞向 M2 表型极化。