Abstract

Objective

The role of microRNAs (miRs) in acute lung injury (ALI) has been discussed. This study is to uncover the effects of miR-146a-3p/Sirtuin-1 (SIRT1)/Nuclear factor-kappa B (NF-κB) axis on ALI.

Methods

Human normal lung epithelial cell line BEAS-2B was exposed to lipopolysaccharide (LPS) to establish an in vitro model of ALI. NF-κB expression, cell activity, apoptosis, inflammatory factors, oxidative stress indices were detected in LPS-induced BEAS-2B cells after miR-146a-3p was down-regulated or SIRT1 was up-regulated. ALI rat model was established and the NF-κB expression, wet/dry weight (W/D) ratio, pathological changes, pneumonocyte apoptosis, inflammatory factors, oxidative stress indices were detected in ALI rats after miR-146a-3p was down-regulated or SIRT1 was up-regulated. The target relationship between miR-146a-3p and SIRT1 was confirmed.

Results

Reduced SIRT1 and raised miR-146a-3p were found in LPS-induced BEAS-2B cells and ALI rats. SIRT1-overexpressing or miR-146a-3p-underexpressing up-regulated NF-κB expression, promoted viability and inhibited apoptosis of LPS-induced BEAS-2B cells in vitro, and increased NF-κB expression, down-regulated the W/D ratio, attenuated pathological changes, suppressed apoptosis, and alleviated inflammatory response and oxidative stress in the lung of ALI rats. MiR-146a-3p directly binds to the 3′UTR of SIRT1 mRNA.

Conclusion

Depleting miR-146a-3p improves ALI through up-regulating SIRT1 and mediating NF-κB pathway.

中文翻译：

---

消耗microRNA-146a-3p通过上调SIRT1和介导NF-κB通路减轻脂多糖诱导的急性肺损伤

摘要

客观的

已经讨论了微小 RNA (miRs) 在急性肺损伤 (ALI) 中的作用。本研究旨在揭示 miR-146a-3p/Sirtuin-1 (SIRT1)/核因子-κB (NF-κB) 轴对 ALI 的影响。

方法

人正常肺上皮细胞系 BEAS-2B 暴露于脂多糖 (LPS) 以建立ALI体外模型。在miR-146a-3p下调或SIRT1上调后，LPS诱导的BEAS-2B细胞中检测到NF-κB表达、细胞活性、细胞凋亡、炎症因子、氧化应激指标。建立ALI大鼠模型,下调miR-146a-3p后,检测ALI大鼠NF-κB表达、湿干重(W/D)比、病理变化、肺细胞凋亡、炎症因子、氧化应激指标或 SIRT1 被上调。miR-146a-3p与SIRT1之间的靶标关系得到证实。

结果

在 LPS 诱导的 BEAS-2B 细胞和 ALI 大鼠中发现 SIRT1 降低和 miR-146a-3p 升高。SIRT1过度表达或miR-146a的-3P-不足的上调NF-κB表达，促进LPS诱导的BEAS-2B细胞的活力和抑制细胞凋亡在体外，和增加的NF-κB表达，下调的W / d比，减轻病理变化，抑制细胞凋亡，减轻 ALI 大鼠肺的炎症反应和氧化应激。MiR-146a-3p 直接与 SIRT1 mRNA 的 3'UTR 结合。

结论

消耗 miR-146a-3p 通过上调 SIRT1 和介导 NF-κB 通路改善 ALI。