Sodium tanshinone IIA sulfonate protects against acute exacerbation of cigarette smoke-induced chronic obstructive pulmonary disease in mice
Sodium tanshinone IIA sulfonate protects against acute exacerbation of cigarette smoke-induced chronic obstructive pulmonary disease in mice
复制标题
丹参酮 IIA 磺酸钠可防止小鼠吸烟引起的慢性阻塞性肺病急性加重
DOI：
10.1016/j.intimp.2020.106261
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发表时间：
2020-04-01
影响因子：
5.6
通讯作者：
Lu, Wenju
中科院分区：
文献类型：
--
作者：
Li, Defu;Sun, Dejun;Lu, Wenju
慢性阻塞性肺疾病(COPD)的加重以急性呼吸道炎症和粘液高分泌为特征，这是迄今为止治疗费用最高的方面。因此，开发低副作用的慢性阻塞性肺疾病急性加重的治疗方法是至关重要的。丹参酮IIA磺酸钠(STS)是丹参酮IIA的水溶性衍生物，是中草药丹参的主要活性成分。尽管STS具有抗炎、抗氧化和抗细胞凋亡的特性，但目前尚不清楚STS是否可以预防COPD的恶化。在这项研究中，我们用脂多糖(LPS)挑战香烟烟雾(CS)暴露的小鼠，然后用STS治疗这些小鼠。我们发现，STS显著改善了CS暴露小鼠的肺炎症反应、粘液高分泌和肺功能下降。STS治疗还可显著减轻香烟烟雾提取物(CSE)刺激的人支气管上皮细胞(16HBE)在内毒素攻击下增加的IL-6和IL-8释放。在机制上，STS降低了CS暴露小鼠和CSE处理的16HBE细胞中ERK1/2和NF-kappaB的活化。综上所述，STS对CS诱导的肺损伤的急性加重有保护作用，这为阻止COPD的急性加重提供了一条有前景和潜在的治疗途径。
Exacerbation of chronic obstructive pulmonary disease (COPD) is characterized by acute airway inflammation and mucus hypersecretion, which is by far the most costly aspect of its management. Thus, it is essential to develop therapeutics with low side effects for CODP exacerbation. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the major active component of Chinese herbal medicine Danshen. Although it possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, it remains unknown whether STS protects against COPD exacerbation. In this study, we challenged cigarette smoke (CS)-exposed mice with lipopolysaccharide (LPS), and then treated these mice with STS. We found that STS significantly ameliorated pulmonary inflammatory responses, mucus hypersecretion and lung function decline in CS-exposed mice challenged with LPS. STS treatment also significantly attenuated increased IL-6 and IL-8 releases from cigarette smoke extract (CSE)-treated human bronchial epithelial cells (16HBE) challenged with LPS. Mechanistically, STS reduced activation of ERK1/2 and NF-kappa B in lungs of CS-exposed mice and CSE-treated 16HBE cells challenged with LPS. Taken together, STS protects against acute exacerbation of CS-induced lung injury, which provides a promising and potential therapeutic avenue to halt acute exacerbation of COPD.