Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China.
Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Inflammation. 2017 Dec;40(6):2062-2073. doi: 10.1007/s10753-017-0646-x.
Pulmonary fibrosis is a life-threatening disease characterized by progressive dyspnea and worsening of pulmonary function. No effective therapeutic strategy for pulmonary fibrosis has been established. Aucubin is a natural constituent with a monoterpene cyclic ring system. The potency of aucubin in protecting cellular components against inflammation, oxidative stress, and proliferation effects is well documented. In this study, we investigated the protective effect of aucubin against pulmonary fibrosis in mice. A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (BLM), and aucubin was administered for 21 days after BLM injection. We found that aucubin decreased the breathing frequency and increased the lung dynamic compliance of BLM-stimulated mice detected by Buxco pulmonary function testing system. Histological examination showed that aucubin alleviated BLM-induced lung parenchymal fibrotic changes. Aucubin also reduced the intrapulmonary collagen disposition and inflammatory injury induced by BLM. In addition, aucubin reduced the expression of pro-fibrotic protein transforming growth factor (TGF)-β1 and α-smooth muscle actin (α-SMA) of pulmonary fibrosis mice induced by BLM. Furthermore, the effect of aucubin on the proliferation and differentiation of fibroblast was investigated in vitro. Aucubin inhibited the mRNA and protein expression of Ki67 and proliferating cell nuclear antigen (PCNA) induced by TGF-β1 and reduced the cell proliferation in a murine fibroblast cell NIH3T3. Aucubin also reduced the collagen syntheses and α-SMA expression induced by TGF-β1 in fibroblast. Our results indicate that aucubin inhibits inflammation, fibroblast proliferation, and differentiation, exerting protective effects against BLM-induced pulmonary fibrosis in a mouse model. This study provides an evidence that aucubin may be a novel drug for pulmonary fibrosis.
肺纤维化是一种危及生命的疾病，其特征是进行性呼吸困难和肺功能恶化。目前尚未建立针对肺纤维化的有效治疗策略。桃叶珊瑚苷是一种具有单萜环系统的天然成分。桃叶珊瑚苷在保护细胞成分免受炎症、氧化应激和增殖作用方面的功效已有充分的文献记载。在这项研究中，我们研究了桃叶珊瑚苷对肺纤维化小鼠的保护作用。通过气管内注射博来霉素（BLM）建立肺纤维化小鼠模型，并在 BLM 注射后给予桃叶珊瑚苷 21 天。我们发现，Buxco 肺功能检测系统检测到，桃叶珊瑚苷可降低 BLM 刺激的小鼠的呼吸频率并增加肺动态顺应性。组织学检查表明，桃叶珊瑚苷可减轻 BLM 诱导的肺实质纤维化变化。桃叶珊瑚苷还减少了 BLM 诱导的肺内胶原分布和炎症损伤。此外，桃叶珊瑚苷降低了 BLM 诱导的肺纤维化小鼠中促纤维化蛋白转化生长因子（TGF）-β1 和α-平滑肌肌动蛋白（α-SMA）的表达。此外，还在体外研究了桃叶珊瑚苷对成纤维细胞增殖和分化的影响。桃叶珊瑚苷抑制 TGF-β1 诱导的 Ki67 和增殖细胞核抗原（PCNA）的 mRNA 和蛋白表达，并减少小鼠成纤维细胞 NIH3T3 的细胞增殖。桃叶珊瑚苷还降低了 TGF-β1 诱导的成纤维细胞胶原合成和α-SMA 表达。我们的结果表明，桃叶珊瑚苷可抑制炎症、成纤维细胞增殖和分化，对 BLM 诱导的肺纤维化小鼠模型发挥保护作用。这项研究为桃叶珊瑚苷可能是一种新型肺纤维化药物提供了证据。
