Neuroinflammation is critical in the pathogenesis of neurological diseases. Microglial pro-inflammatory (M1) and anti-inflammatory (M2) status determines the outcome of neuroinflammation. Dexmedetomidine exerts anti-inflammatory effects in many neurological conditions. Whether dexmedetomidine functions via modulation of microglia M1/M2 polarization remains to be fully elucidated. In the present study, we investigated the anti-inflammatory effects of dexmedetomidine on the neuroinflammatory cell model and explored the potential mechanism. BV2 cells were stimulated with LPS to establish a neuroinflammatory model. The cell viability was determined with MTT assay. NO levels were assessed using a NO detection kit. The protein levels of IL-10, TNF-α, iNOS, CD206, ERK1/2, and pERK1/2 were quantified using Western blotting. LPS significantly increased pro-inflammatory factors TNF-α and NO, and M1 phenotypic marker iNOS, and decreased anti-inflammatory factor IL-10 and M2 phenotypic marker CD206 in BV2 cells. Furthermore, exposure of BV2 cells to LPS significantly raised pERK1/2 expression. Pretreatment with dexmedetomidine attenuated LPS-elicited changes in p-ERK, iNOS, TNF-α, NO, CD206 and IL-10 levels in BV2 cells. However, co-treatment with dexmedetomidine and LM22B-10, an agonist of ERK, reversed dexmedetomidine-elicited changes in p-ERK, iNOS, TNF-α, NO, CD206 and IL-10 levels in LPS-exposed BV2 cells. We, for the first time, showed that dexmedetomidine increases microglial M2 polarization by inhibiting phosphorylation of ERK1/2, by which it exerts anti-inflammatory effects in BV2 cells.

中文翻译：

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右美托咪定通过通过MAPK / ERK途径改变小胶质细胞M1 / M2极化来抑制神经炎症。

神经炎症在神经系统疾病的发病机理中至关重要。小胶质细胞的促炎（M1）和抗炎（M2）状态决定了神经炎症的结局。右美托咪定在许多神经系统疾病中发挥抗炎作用。右美托咪定是否通过调节小胶质细胞M1 / M2极化而起作用。在本研究中，我们研究了右美托咪定对神经炎细胞模型的抗炎作用，并探讨了其潜在机制。用LPS刺激BV2细胞建立神经炎症模型。用MTT测定法测定细胞活力。使用NO检测试剂盒评估NO水平。使用蛋白质印迹法定量测定IL-10，TNF-α，iNOS，CD206，ERK1 / 2和pERK1 / 2的蛋白水平。LPS显着增加BV2细胞中促炎因子TNF-α和NO以及M1表型标志物iNOS，并降低抗炎因子IL-10和M2表型标志物CD206。此外，将BV2细胞暴露于LPS会显着提高pERK1 / 2表达。右美托咪定预处理可减轻LPS引起的BV2细胞中p-ERK，iNOS，TNF-α，NO，CD206和IL-10水平的变化。但是，与右美托咪定和ERK的激动剂LM22B-10共同治疗可逆转右美托咪啶引起的LPS暴露BV2细胞中p-ERK，iNOS，TNF-α，NO，CD206和IL-10的变化。我们首次表明，右美托咪定通过抑制ERK1 / 2的磷酸化增加小胶质细胞M2极化，从而在BV2细胞中发挥抗炎作用。并降低BV2细胞中的抗炎因子IL-10和M2表型标记CD206。此外，将BV2细胞暴露于LPS会显着提高pERK1 / 2表达。右美托咪定预处理可减轻LPS引起的BV2细胞中p-ERK，iNOS，TNF-α，NO，CD206和IL-10水平的变化。但是，与右美托咪定和ERK的激动剂LM22B-10共同治疗可逆转右美托咪啶引起的LPS暴露BV2细胞中p-ERK，iNOS，TNF-α，NO，CD206和IL-10的变化。我们首次表明，右美托咪定通过抑制ERK1 / 2的磷酸化增加小胶质细胞M2极化，从而在BV2细胞中发挥抗炎作用。并降低BV2细胞中的抗炎因子IL-10和M2表型标记CD206。此外，将BV2细胞暴露于LPS会显着提高pERK1 / 2表达。右美托咪定预处理可减轻LPS引起的BV2细胞中p-ERK，iNOS，TNF-α，NO，CD206和IL-10水平的变化。但是，与右美托咪定和ERK的激动剂LM22B-10共同治疗可逆转右美托咪啶引起的LPS暴露BV2细胞中p-ERK，iNOS，TNF-α，NO，CD206和IL-10的变化。我们首次表明，右美托咪定通过抑制ERK1 / 2的磷酸化增加小胶质细胞M2极化，从而在BV2细胞中发挥抗炎作用。右美托咪定预处理可减轻LPS引起的BV2细胞中p-ERK，iNOS，TNF-α，NO，CD206和IL-10水平的变化。但是，与右美托咪定和ERK的激动剂LM22B-10共同治疗可逆转右美托咪啶引起的LPS暴露BV2细胞中p-ERK，iNOS，TNF-α，NO，CD206和IL-10的变化。我们首次表明，右美托咪定通过抑制ERK1 / 2的磷酸化增加小胶质细胞M2极化，从而在BV2细胞中发挥抗炎作用。右美托咪定预处理可减轻LPS引起的BV2细胞中p-ERK，iNOS，TNF-α，NO，CD206和IL-10水平的变化。但是，与右美托咪定和ERK的激动剂LM22B-10共同治疗可逆转右美托咪啶引起的LPS暴露BV2细胞中p-ERK，iNOS，TNF-α，NO，CD206和IL-10的变化。我们首次表明，右美托咪定通过抑制ERK1 / 2的磷酸化增加小胶质细胞M2极化，从而在BV2细胞中发挥抗炎作用。