Aucubin Alleviates Bleomycin-Induced Pulmonary Fibrosis in a Mouse Model
Aucubin Alleviates Bleomycin-Induced Pulmonary Fibrosis in a Mouse Model
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Aucubin 可减轻小鼠模型中博来霉素诱导的肺纤维化
DOI：
10.1007/s10753-017-0646-x
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发表时间：
2017-12-01
期刊：
影响因子：
5.1
通讯作者：
Guan, Cha-Xiang
中科院分区：
文献类型：
--
作者：
Zhou, Yong;Li, Ping;Guan, Cha-Xiang
肺纤维化是一种以进行性呼吸困难和肺功能恶化为特征的危及生命的疾病。尚未建立有效的肺纤维化治疗策略。桃叶珊瑚甙是一种天然单萜环化合物。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效力是有据可查的。在这项研究中，我们研究了桃叶珊瑚苷对小鼠肺纤维化的保护作用。采用博莱霉素（BLM）腹腔注射建立小鼠肺纤维化模型，并于BLM注射后给予桃叶珊瑚甙21天。Buxco肺功能测定系统检测发现桃叶珊瑚苷能降低BLM刺激小鼠的呼吸频率，增加肺动态顺应性。组织学检查显示桃叶珊瑚甙减轻BLM诱导的肺实质纤维化改变。桃叶珊瑚甙还能减轻BLM引起的肺内胶原沉积和炎性损伤。桃叶珊瑚苷还能降低BLM诱导的肺纤维化小鼠肺组织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，在体外研究桃叶珊瑚甙对成纤维细胞增殖和分化的影响。桃叶珊瑚苷可抑制TGF-β1诱导的小鼠成纤维细胞NIH 3 T3增殖，抑制Ki 67和增殖细胞核抗原（PCNA）的表达。桃叶珊瑚苷还能抑制TGF-β1诱导的成纤维细胞胶原合成和α-SMA表达。我们的研究结果表明，桃叶珊瑚苷抑制炎症，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。本研究为桃叶珊瑚苷可能成为治疗肺纤维化的新药提供了依据。
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 investigatedin 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.