The process of neurodegenerative diseases has always been accompanied by neuroinflammatory response characterized by microglia activation. Two phenotypes of microglial polarization: the classically activated M1 type and the alternative activated M2 type, have been described. Although apelin-13 has been shown to have neuroprotective effects, its specific mechanism of anti-neuritis is still unclear. The aim of this study was to investigate whether apelin-13 can exert anti-neuroinflammatory effects by regulating the polarization of N9 microglia. MTT assay showed that 0.1 μM apelin-13 (24 h) and 2 μg/mL LPS (6 h) treatment had no significant effect on cell viability of N9 microglia. The combined treatment of Apelin-13 and LPS did not affect the viability of N9 microglia. N9 microglia were pretreated with 0.1 μM apelin-13 for 24 h, followed by incubation with LPS for 6 h. Morphological results indicated that apelin-13 (0.1 μM) inhibited LPS-induced N9 microglial activation as observed by smaller soma and slender process compared to LPS-treated group. Western blot confirmed that apelin-13 decreased the level of proinflammatory factor iNOS, IL-6 and up-regulated the level of anti-inflammatory factor arg-1 and IL-10 in N9 microglia. Flow cytometry revealed that apelin-13 inhibited the expression of M1 microglia activation marker CD86 and up-regulated the expression of M2 marker CD206. Furthermore, the data displayed that apelin-13 decreased the expression of p-STAT3 and the radio of p-STAT3/t-STAT3 in M1-type N9 microglia induced by LPS. In conclusion, our results indicated apelin-13 ameliorated neuroinflammation by shifting N9 microglial M1 polarization toward the M2 phenotype, the underlying mechanism of which may be related to STAT3 signals.

中文翻译：

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Apelin-13 调控 LPS 诱导的 N9 小胶质细胞极化，涉及 STAT3 信号通路

神经退行性疾病的过程一直伴随着以小胶质细胞激活为特征的神经炎症反应。小胶质细胞极化的两种表型：经典激活 M1 型和替代激活 M2 型，已被描述。虽然apelin-13已被证明具有神经保护作用，但其抗神经炎的具体机制仍不清楚。本研究的目的是研究apelin-13是否可以通过调节N9小胶质细胞的极化来发挥抗神经炎症作用。MTT 测定表明，0.1 μM apelin-13（24 小时）和 2 μg/mL LPS（6 小时）处理对 N9 小胶质细胞的细胞活力没有显着影响。Apelin-13 和 LPS 的联合处理不影响 N9 小胶质细胞的活力。N9 小胶质细胞用 0.1 μM apelin-13 预处理 24 h，然后用 LPS 孵育 6 小时。形态学结果表明，与 LPS 处理组相比，apelin-13 (0.1 μM) 抑制了 LPS 诱导的 N9 小胶质细胞活化，如通过更小的体细胞和细长的突起所观察到的。Western blot证实apelin-13降低了N9小胶质细胞中促炎因子iNOS、IL-6的水平，上调了抗炎因子arg-1和IL-10的水平。流式细胞术显示apelin-13抑制M1小胶质细胞活化标志物CD86的表达并上调M2标志物CD206的表达。此外，数据显示apelin-13降低了LPS诱导的M1型N9小胶质细胞中p-STAT3的表达和p-STAT3/t-STAT3的放射。综上所述，