Objective and design

This study aimed to investigate the anti-pulmonary inflammation effect of emodin on Wistar rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI) and RAW264.7 cells through the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway.

Subjects

Wistar rats and RAW264.7 cells were studied.

Treatment

LPS was used to induce inflammation in rats or RAW264.7 cells and emodin was given once a day before LPS stimulation and continued for a certain number of days.

Methods

Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for the in vivo experiment, while cells and supernatant were collected for the in vitro experiment. Pathological changes in the lung tissues were assessed by hematoxylin and eosin staining. The levels of inflammatory factors, including TNF-α, IL-1β, and IL-6, were determined by enzyme-linked immunosorbent assay. The expression levels of p-mTOR, HIF-1α, and VEGF proteins were measured by Western blot analysis and immunohistochemistry. The mRNA levels of p70S6K, eIF4E-BP1, and eIF4E were measured by quantitative polymerase chain reaction.

Results

Emodin ameliorated pathological changes and infiltrated inflammatory cells in LPS-induced ALI. It also significantly reduced the expression of inflammatory factors, including TNF-α, IL-1β, and IL-6, in BALF and downregulated the expression of p-mTOR, HIF-1α, and VEGF proteins in the lung tissues. Similar anti-inflammatory effects and the downregulation of the mTOR/HIF-1α/VEGF signaling pathway were found in RAW264.7 cells. The mRNA levels of p70S6K, eIF4E-BP1, and eIF4E also decreased in the macrophages.

Conclusion

Emodin alleviated LPS-induced pulmonary inflammation in rat lung tissues and RAW264.7 cells through inhibiting the mTOR/HIF-1α/VEGF signaling pathway, which accounted for the therapeutic effects of emodin on ALI.

中文翻译：

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大黄素通过抑制mTOR /HIF-1α/ VEGF信号通路减轻LPS诱发的急性肺损伤大鼠的肺部炎症。

目标和设计

这项研究旨在探讨大黄素通过哺乳动物雷帕霉素（mTOR）/低氧诱导因子-1α对脂多糖（LPS）诱导的急性肺损伤（ALI）和RAW264.7细胞的Wistar大鼠的抗肺炎症作用（HIF-1α）/血管内皮生长因子（VEGF）信号通路。

科目

研究了Wistar大鼠和RAW264.7细胞。

治疗

LPS用于诱导大鼠或RAW264.7细胞发炎，大黄素在LPS刺激之前每天给药一次，并持续一定天数。

方法

收集肺组织和支气管肺泡灌洗液（BALF）进行体内实验，同时收集细胞和上清液进行体外实验。通过苏木精和曙红染色评估肺组织的病理变化。通过酶联免疫吸附法测定炎症因子的水平，包括TNF-α，IL-1β和IL-6。通过蛋白质印迹分析和免疫组化检测p-mTOR，HIF-1α和VEGF蛋白的表达水平。通过定量聚合酶链反应测量p70S6K，eIF4E-BP1和eIF4E的mRNA水平。

结果

大黄素改善了LPS诱导的ALI的病理变化和炎性细胞浸润。它还显着降低了BALF中炎性因子（包括TNF-α，IL-1β和IL-6）的表达，并下调了肺组织中p-mTOR，HIF-1α和VEGF蛋白的表达。在RAW264.7细胞中发现了类似的抗炎作用以及mTOR /HIF-1α/ VEGF信号通路的下调。在巨噬细胞中，p70S6K，eIF4E-BP1和eIF4E的mRNA水平也下降。

结论

大黄素通过抑制mTOR /HIF-1α/ VEGF信号通路减轻LPS诱导的大鼠肺组织和RAW264.7细胞的肺部炎症，这是大黄素对ALI的治疗作用。