METHODS: Mouse models of IPF were divided into four treatment groups: control, bleomycin (BLM), quercetin (Q), and quercetin + EX-527 (Q + E) treatment. Pulmonary fibrosis was induced in the mouse models through intratracheal instillation of BLM. Various indexes were identified through histological staining, Western blotting analysis, enzyme-linked immunosorbent assay, immunohistochemistry, and transmission electron microscopy.
RESULTS: Quercetin treatment ameliorated the pathology of BLM-induced pulmonary fibrosis of mice by reducing α-smooth muscle actin (α-SMA), collagen I (Col I), and collagen III (Col III) levels, and also improved the level of E-cadherin in lung tissue. Furthermore, Quercetin significantly enhanced LC3II/LC3I levels, decreased P62 expression, and increased the number of autophagosomes in lung tissue. These effects were accompanied by the activation of the SIRT1/AMPK pathway. Treatment with EX-527, an inhibitor for SIRT1, reversed all effects induced by quercetin.
CONCLUSIONS: This study showed that quercetin could alleviate pulmonary fibrosis and improve epithelial-mesenchymal transition by acting on the SIRT1/AMPK signaling pathway, which may be achieved by regulating the level of autophagy.
方法:将IPF小鼠模型分为四个治疗组:对照组,博来霉素(BLM),槲皮素(Q),和槲皮素+EX-527(Q+E)处理。通过气管内滴注BLM在小鼠模型中诱导肺纤维化。通过组织学染色鉴定各种指标,蛋白质印迹分析,酶联免疫吸附测定,免疫组织化学,和透射电子显微镜。
结果:槲皮素治疗通过减少α-平滑肌肌动蛋白(α-SMA)改善BLM诱导的小鼠肺纤维化的病理,胶原蛋白I(ColI),和胶原蛋白III(ColIII)水平,并提高了肺组织中E-cadherin的水平。此外,槲皮素显著提高LC3II/LC3I水平,P62表达降低,并增加肺组织中自噬体的数量。这些作用伴随着SIRT1/AMPK途径的激活。用EX-527(SIRT1的抑制剂)治疗可逆转槲皮素诱导的所有作用。
结论:本研究表明槲皮素可通过作用于SIRT1/AMPK信号通路,减轻肺纤维化,改善上皮间质转化,这可以通过调节自噬水平来实现。