长链非编码 RNA PADNA 的敲低通过 miR-194/FBXW7 轴促进布比卡因诱导的神经毒性。

Knockdown of lincRNA PADNA promotes bupivacaine-induced neurotoxicity by miR-194/FBXW7 axis.

机构信息

Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Henan, China.

Department of Anesthesiology, The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China.

出版信息

Mol Med. 2020 Aug 13;26(1):79. doi: 10.1186/s10020-020-00209-8.

BACKGROUND

The aim of the study was to explore the function and mechanism of lincRNA PADNA in bupivacaine-induced neurotoxicity.

METHODS

Mouse DRG neurons were cultured in vitro and treated with bupivacaine to establish a neurotoxicity model. Caspase3 activity, cell viability, and TUNEL assays were analyzed to assess the role of lincRNA PADNA. A dual-luciferase reporter assay was used to determine the binding target of lincRNA PANDA.

RESULTS

The expression of lincRNA PADNA was significantly increased with increasing concentrations of bupivacaine. Functional analysis revealed that knockdown of lincRNA PADNA increased caspase3 activity and inhibited cell viability. Western blot analysis showed that knockdown of lincRNA PADNA promoted cleaved caspase3 levels. We also revealed that lincRNA PADNA may bind with miR-194. Knockdown of miR-194 rescued the function of lincRNA PADNA, suggesting that lincRNA PADNA may sponge miR-194. In addition, we provided new evidence that the lincRNA PADNA/miR-194/FBXW7 axis plays an important role in the neurotoxicity process.

CONCLUSION

We performed comprehensive experiments to verify the function and mechanism of lincRNA PADNA in bupivacaine-induced neurotoxicity. Our study provides new evidence and clues for the prevention of neurotoxicity.

背景

本研究旨在探讨 lincRNA PADNA 在布比卡因诱导的神经毒性中的作用和机制。

方法

体外培养小鼠背根神经节神经元并给予布比卡因处理，建立神经毒性模型。通过 caspase3 活性、细胞活力和 TUNEL 检测分析来评估 lincRNA PADNA 的作用。采用双荧光素酶报告基因实验来确定 lincRNA PANDA 的结合靶标。

结果

随着布比卡因浓度的增加，lincRNA PADNA 的表达明显增加。功能分析显示，lincRNA PADNA 敲低可增加 caspase3 活性并抑制细胞活力。Western blot 分析显示，lincRNA PADNA 敲低可促进 cleaved caspase3 水平的增加。我们还发现 lincRNA PADNA 可能与 miR-194 结合。miR-194 的敲低挽救了 lincRNA PADNA 的功能，表明 lincRNA PADNA 可能作为 miR-194 的海绵。此外，我们提供了新的证据表明 lincRNA PADNA/miR-194/FBXW7 轴在神经毒性过程中发挥重要作用。