Abstract：
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by a constant incidence rate. Unfortunately, effective pharmacological treatments for this condition are lacking and the identification of novel therapeutic approaches and underlying pathological mechanisms are required. This study investigated the potential of quercetin in alleviating pulmonary fibrosis by promoting autophagy and activation of the SIRT1/AMPK pathway.
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.
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.
摘要：
背景：特发性肺纤维化（IPF）是一种病因不明的疾病，其特征是发病率恒定。不幸的是,这种情况缺乏有效的药物治疗方法，需要确定新的治疗方法和潜在的病理机制。本研究探讨槲皮素通过促进自噬和激活SIRT1/AMPK通路减轻肺纤维化的潜力。
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。
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。
