ABSTRACT

Tang-luo-ning (TLN) is a traditional Chinese herbal recipe that has been used to treat diabetic peripheral neuropathy (DPN); nevertheless, the underlying mechanism remains unclear. This study was aimed to investigate the microRNA (miRNA) expression profile in diabetic rats treated with TLN, and the target genes were predicted. Male Sprague-Dawley rats were randomly divided into control, diabetes, and TLN-treated diabetes groups. Diabetes was induced with streptozotocin, and TLN (5 g/kg/day) was orally given for eight weeks. Then, the sciatic nerves were harvested for miRNA microarray analyses. The differentially expressed miRNAs and their target genes were analyzed. Compared with the control rats, 24 miRNAs were significantly upregulated, and 59 were downregulated in the sciatic nerves of the diabetic rats by more than two folds (all P < 0.05). In TLN-treated diabetes rats, 26 miRNAs were upregulated, and 14 were downregulated compared with diabetic rats without TLN treatment (all P < 0.05). DPN-induced alterations of the miRNA profile were reversed by the TLN treatment. A total of 1402 target genes were screened. In GO analysis, genes in localization, cytoplasm, and protein binding processes were enriched, and the most significantly enriched pathways included the neurotrophin, Fc epsilon RI, and Wnt signaling pathways. Further analyses revealed that DVL1 and NTF3 genes were involved in these pathways. Our findings indicate that TLN may affect the Wnt and neurotrophin pathways by acting on DVL1 and NTF3 genes.

摘要

汤洛宁（TLN）是一种传统的中草药方，用于治疗糖尿病周围神经病变（DPN）；尽管如此，其潜在机制仍不清楚。本研究旨在研究 TLN 治疗的糖尿病大鼠的 microRNA (miRNA) 表达谱，并预测目标基因。雄性 Sprague-Dawley 大鼠随机分为对照组、糖尿病组和 TLN 治疗的糖尿病组。用链脲佐菌素诱导糖尿病，并口服 TLN（5 g/kg/天）8 周。然后，收集坐骨神经用于 miRNA 微阵列分析。分析差异表达的miRNA及其靶基因。与对照组相比，糖尿病大鼠坐骨神经中24个miRNAs显着上调，59个miRNAs下调2倍以上（均为P < 0.05)。与未经 TLN 治疗的糖尿病大鼠相比，在 TLN 治疗的糖尿病大鼠中，26 个 miRNA 上调，14 个下调（均P < 0.05）。TLN 处理逆转了 DPN 诱导的 miRNA 谱的改变。共筛选了1402个靶基因。在 GO 分析中，定位、细胞质和蛋白质结合过程中的基因被富集，最显着富集的通路包括神经营养因子、Fc epsilon RI 和 Wnt 信号通路。进一步的分析表明DVL1和NTF3基因参与这些途径。我们的研究结果表明，TLN 可能通过作用于DVL1和NTF3基因来影响 Wnt 和神经营养因子途径。