Emodin alleviates bleomycin-induced pulmonary fibrosis in rats
Emodin alleviates bleomycin-induced pulmonary fibrosis in rats
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大黄素减轻博莱霉素诱导的大鼠肺纤维化
DOI：
10.1016/j.toxlet.2016.10.004
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发表时间：
2016-11-16
影响因子：
3.5
通讯作者：
Shen, Linlin
中科院分区：
文献类型：
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作者：
Guan, Ruijuan;Zhao, Xiaomei;Shen, Linlin
特发性肺纤维化（IPF）是一种致命的肺部疾病，治疗选择很少且预后不良。从大黄中提取的大黄素被发现能够减轻博莱霉素（BLM）引起的肺纤维化，但其潜在机制仍不清楚。本研究旨在进一步探讨大黄素对BLM诱导的大鼠肺纤维化炎症和纤维化的影响及其机制。我们的结果表明，大黄素可以改善 BLM 治疗大鼠的肺功能、减少体重减轻并防止死亡。大黄素显着缓解肺水肿和纤维化变化，减少胶原沉积，抑制肌成纤维细胞[以α平滑肌肌动蛋白（α-SMA）表达为特征]和炎症细胞（主要是巨噬细胞和淋巴细胞）的浸润。此外，大黄素降低了 BLM 治疗大鼠肺部 TNF-α、IL-6、TGF-β1 和热休克蛋白 (HSP)-47 的水平。在体外，大黄素显着抑制 TGF-β1 诱导的人胚胎肺成纤维细胞 (HELF) 中 α-SMA、IV 型胶原蛋白和纤连蛋白的表达。大黄素还抑制 TGF-β 1 诱导的 Smad2/3 和 STAT3 激活，表明 Smad2/3 和 STAT3 失活介导大黄素诱导的对 TGF-β 1 诱导的肌成纤维细胞分化的影响。这些结果表明，大黄素可以通过抑制 TGF-β1 信号传导并随后抑制炎症、HSP-47 表达、肌成纤维细胞分化和细胞外基质 (ECM) 沉积来发挥其抗纤维化作用。 (C) 2016 Elsevier Ireland Ltd. 保留所有权利。
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with few treatment options and poor prognosis. Emodin, extracted from Chinese rhubarb, was found to be able to alleviate bleomycin (BLM)-induced pulmonary fibrosis, yet the underlying mechanism remains largely unknown. This study aimed to further investigate the effects of emodin on the inflammation and fibrosis of BLM-induced pulmonary fibrosis and the mechanism involved in rats. Our results showed that emodin improved pulmonary function, reduced weight loss and prevented death in BLM-treated rats. Emodin significantly relieved lung edema and fibrotic changes, decreased collagen deposition, and suppressed the infiltration of myofibroblasts [characterized by expression of alpha-smooth muscle actin (alpha-SMA)] and inflammatory cells (mainly macrophages and lymphocytes). Moreover, emodin reduced levels of TNF-alpha, IL-6, TGF-beta 1 and heat shock protein (HSP)-47 in the lungs of BLM-treated rats. In vitro, emodin profoundly inhibited TGF-beta 1-induced alpha-SMA, collagen IV and fibronectin expression in human embryo lung fibroblasts (HELFs). Emodin also inhibited TGF-beta 1-induced Smad2/3 and STAT3 activation, indicating that Smad2/3 and STAT3 inactivation mediates emodin-induced effects on TGF-beta 1-induced myofibroblast differentiation. These results suggest that emodin can exert its anti-fibrotic effect via suppression of TGF-beta 1 signaling and subsequently inhibition of inflammation, HSP-47 expression, myofibroblast differentiation and extracellular matrix (ECM) deposition. (C) 2016 Elsevier Ireland Ltd. All rights reserved.