Objective. To probe into the role of miR-92a in alleviating oxidative stress and apoptosis of alveolar epithelial cell (AEC) injury induced by lipopolysaccharide (LPS) exposure through the Toll-like receptor (TLR) 2/activator protein-1 (AP-1) pathway. Methods. Acute lung injury (ALI) rat model and ALI alveolar epithelial cell model were constructed to inhibit the expression of miR-92a/TLR2/AP-1 in rat and alveolar epithelial cells (AECs), to detect the changes of oxidative stress, inflammatory response, and cell apoptosis in rat lung tissues and AECs, and to measure the changes of wet-dry weight (W/D) ratio in rat lung tissues. Results. Both inhibition of miR-92a expression and knockout of TLR2 and AP-1 gene could reduce LPS-induced rat ALI, alleviate pulmonary edema, inhibit oxidative stress and inflammatory response, and reduce apoptosis of lung tissue cells. In addition, the TLR2 and AP-1 levels in the lung tissues of ALI rats were noticed to be suppressed when inhibiting the expression of miR-92a, and the AP-1 level was also decreased after the knockout of TLR2 gene. Further, we verified this relationship in AECs and found that inhibition of miR-92a/TLR2/AP-1 also alleviated LPS-induced AEC injury, reduced cell apoptosis, and inhibited oxidative stress and inflammatory response. What is more, like that in rat lung tissue, the phenomenon also existed in AECs, that is, when the expression of miR-92a was inhibited, the expression of TLR2 and AP-1 was inhibited, and silencing TLR2 can reduce the expression level of AP-1. Conclusion. MiR-92a/TLR2/AP-1 is highly expressed in ALI, and its inhibition can improve oxidative stress and inflammatory response and reduce apoptosis of AECs.

中文翻译：

---

抑制 Mir-92a 通过 TLR2/AP-1 途径减轻脂多糖暴露诱导的氧化应激和肺泡上皮细胞凋亡


客观的。探讨miR-92a通过Toll样受体(TLR)2/激活蛋白-1(AP-1)减轻脂多糖(LPS)暴露引起的肺泡上皮细胞(AEC)损伤的氧化应激和凋亡的作用途径。方法。构建急性肺损伤（ALI）大鼠模型及ALI肺泡上皮细胞模型，抑制大鼠及肺泡上皮细胞（AECs）miR-92a/TLR2/AP-1的表达，检测氧化应激、炎症反应的变化，以及大鼠肺组织和AEC中的细胞凋亡，并测量大鼠肺组织的湿干重（W/D）比的变化。结果。抑制miR-92a表达以及敲除TLR2和AP-1基因均可减轻LPS诱导的大鼠ALI，减轻肺水肿，抑制氧化应激和炎症反应，减少肺组织细胞凋亡。此外，抑制miR-92a表达时，ALI大鼠肺组织中TLR2和AP-1水平受到抑制，敲除TLR2基因后AP-1水平也降低。此外，我们在 AEC 中验证了这种关系，发现抑制 miR-92a/TLR2/AP-1 也能减轻 LPS 诱导的 AEC 损伤，减少细胞凋亡，并抑制氧化应激和炎症反应。更重要的是，与大鼠肺组织中的情况一样，AECs中也存在这种现象，即当抑制miR-92a的表达时，TLR2和AP-1的表达受到抑制，沉默TLR2可以降低表达水平AP-1 的。结论。 MiR-92a/TLR2/AP-1在ALI中高表达，其抑制可改善氧化应激和炎症反应，减少AECs的凋亡。