Research Centre on Application of Classical Prescriptions, Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Department of Febrile Disease, Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Inflamm Res. 2020 Apr;69(4):365-373. doi: 10.1007/s00011-020-01331-3. Epub 2020 Mar 4.
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.
Wistar rats and RAW264.7 cells were studied.
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.
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.
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.
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.
本研究旨在通过哺乳动物雷帕霉素靶蛋白（mTOR）/低氧诱导因子-1α（HIF-1α）/血管内皮生长因子（VEGF）信号通路，研究大黄素对脂多糖（LPS）诱导的急性肺损伤（ALI）Wistar 大鼠和 RAW264.7 细胞的抗肺炎症作用。
研究了 Wistar 大鼠和 RAW264.7 细胞。
用 LPS 诱导大鼠或 RAW264.7 细胞炎症，大黄素在 LPS 刺激前每天给药一次，并持续一定天数。
进行体内实验时收集肺组织和支气管肺泡灌洗液（BALF），进行体外实验时收集细胞和上清液。通过苏木精和伊红染色评估肺组织的病理变化。通过酶联免疫吸附试验测定 TNF-α、IL-1β 和 IL-6 等炎症因子的水平。通过 Western blot 分析和免疫组织化学测定 p-mTOR、HIF-1α 和 VEGF 蛋白的表达水平。通过定量聚合酶链反应测定 p70S6K、eIF4E-BP1 和 eIF4E 的 mRNA 水平。
大黄素改善了 LPS 诱导的 ALI 中的病理变化和浸润性炎症细胞。它还显著降低了 BALF 中炎症因子（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 细胞中也发现了类似的抗炎作用和 mTOR/HIF-1α/VEGF 信号通路的下调。巨噬细胞中 p70S6K、eIF4E-BP1 和 eIF4E 的 mRNA 水平也降低。
大黄素通过抑制 mTOR/HIF-1α/VEGF 信号通路缓解 LPS 诱导的大鼠肺组织和 RAW264.7 细胞的肺炎症，这解释了大黄素对 ALI 的治疗作用。
