Exposure to organic solvent in industry, including n-hexane is correlated with central-peripheral axonopathy, which is mediated by its active metabolite, 2,5-hexanedione (HD). However, the underlying mechanism is still largely unknown. Recently identified microRNAs (miRNAs) may play important roles in toxicant exposure and in the process of toxicant-induced neuropathys. To examine the role of miRNAs in HD-induced toxicity, neuropathic animal model was successfully built. miRNA microarray analysis revealed 105 differentially expressed miRNAs after HD exposure. Bioinformatics analysis showed that "Axon" and "Neurotrophin Signaling Pathway" was the top significant GO term and pathway, respectively. 7 miRNAs both related to "Axon" and "Neurotrophin Signaling Pathway" were screened out and further confirmed by Real-Time PCR. Correspondingly, the deregulation expression levels of proteins of four target genes (GSK3β, Map3k1, BDNF and MAP1B) were further confirmed via western blot, verifying the results of gene target analysis. Taken together, our results showed that the axon-related miRNAs to be associated with MAP1B or neurotrophin signal pathways changed in nerve tissues following HD exposure. These miRNAs may play important roles in HD-induced neurotoxicity.

中文翻译：

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2,5-己二酮诱导大鼠神经组织中轴突相关微小RNA表达的失调

工业中暴露于有机溶剂，包括正己烷与中枢-外周轴突病相关，后者由其活性代谢物 2,5-己二酮 (HD) 介导。然而，其潜在机制在很大程度上仍是未知的。最近发现的微小RNA（miRNA）可能在毒物暴露和毒物诱导的神经病变过程中发挥重要作用。为了检查 miRNA 在 HD 诱导的毒性中的作用，成功建立了神经性动物模型。miRNA 微阵列分析揭示了 HD 暴露后 105 种差异表达的 miRNA。生物信息学分析表明，“Axon”和“Neurotrophin Signaling Pathway”分别是最重要的 GO 术语和通路。7 种与“轴突”和“神经营养蛋白信号通路”相关的 miRNA 被筛选出来并通过实时 PCR 进一步确认。相应地，通过蛋白质印迹进一步证实了四种靶基因（GSK3β、Map3k1、BDNF和MAP1B）的蛋白质表达水平失调，验证了基因靶点分析的结果。总之，我们的结果表明，与 MAP1B 或神经营养因子信号通路相关的轴突相关 miRNA 在 HD 暴露后在神经组织中发生了变化。这些 miRNA 可能在 HD 诱导的神经毒性中发挥重要作用。我们的结果表明，与 MAP1B 或神经营养因子信号通路相关的轴突相关 miRNA 在 HD 暴露后在神经组织中发生了变化。这些 miRNA 可能在 HD 诱导的神经毒性中发挥重要作用。我们的结果表明，与 MAP1B 或神经营养因子信号通路相关的轴突相关 miRNA 在 HD 暴露后在神经组织中发生了变化。这些 miRNA 可能在 HD 诱导的神经毒性中发挥重要作用。