Abstract：
Scutellarin is an herbal agent which can exert anti-neuroinflammatory effects in activated microglia. However, it remains uncertain if it can inhibit microglia-mediated neuroinflammation by regulating miRNAs. This study sought to elucidate the upstream regulatory mechanisms by endogenous microRNAs and its target gene in activated microglia in lipopolysaccharide (LPS)-induced BV-2 microglia. Results show that scutellarin suppressed the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS) significantly in LPS-stimulated BV-2 microglia. As with the results of miRNAs function classification in vitro, the expression levels of mir-7036a-5p are upregulated in LPS-activated BV-2 microglia, but are downregulated by scutellarin. Rescue experiments indicated that mir-7036a-5p is a pro-inflammatory factor in activated BV-2 microglia. mir-7036a-5p agomir promoted the expression of phosphorylated tau proteins (p-tau), protein kinase C gamma type (PRKCG), extracellular regulated protein kinases (ERK1/2), but the is reversed by mir-7036a-5p antagomir in vitro. It is shown here that mir-7036a-5p is involved in microglia-mediated inflammation in LPS-induced BV-2 microglia. More important is the novel finding that scutellarin mitigated microglia inflammation by down-regulating the mir-7036a-5p/MAPT/PRKCG/ERK signaling pathway.
摘要：
灯盏乙素是一种可以在活化的小胶质细胞中发挥抗神经炎作用的草药。然而,目前尚不清楚它是否可以通过调节miRNAs抑制小胶质细胞介导的神经炎症。本研究旨在阐明脂多糖（LPS）诱导的BV-2小胶质细胞中内源性microRNA及其靶基因在活化小胶质细胞中的上游调控机制。结果表明灯盏乙素抑制肿瘤坏死因子-α(TNF-α)的表达,白细胞介素-1β（IL-1β），在LPS刺激的BV-2小胶质细胞中，诱导型一氧化氮合酶（iNOS）显着。与体外miRNA功能分类的结果一样，在LPS激活的BV-2小胶质细胞中mir-7036a-5p的表达水平上调，但被scutellarin下调。挽救实验表明mir-7036a-5p是活化的BV-2小胶质细胞中的促炎因子。mir-7036a-5pagomir促进磷酸化tau蛋白（p-tau）的表达，蛋白激酶Cγ型（PRKCG），细胞外调节蛋白激酶（ERK1/2），但它在体外被mir-7036a-5pantagomir逆转。此处显示mir-7036a-5p参与LPS诱导的BV-2小胶质细胞中的小胶质细胞介导的炎症。更重要的是新发现，灯盏乙素通过下调mir-7036a-5p/MAPT/PRKCG/ERK信号通路减轻小胶质细胞炎症。
