State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, PR China; The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, PR China.
Departments of Respiratory and Critical Diseases, Inner Mongolia Autonomous Region People's Hospital, Hohhot, PR China.
Int Immunopharmacol. 2020 Apr;81:106261. doi: 10.1016/j.intimp.2020.106261. Epub 2020 Feb 12.
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-κB 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.
慢性阻塞性肺疾病（COPD）的恶化特征为急性气道炎症和黏液高分泌，这是其治疗费用最昂贵的方面。因此，开发具有低副作用的 COPD 恶化治疗方法至关重要。丹参酮 IIA 磺酸钠（STS）是丹参中主要活性成分的水溶性衍生物，具有抗炎、抗氧化和抗凋亡作用。尽管如此，STS 是否能预防 COPD 恶化仍不清楚。在这项研究中，我们用脂多糖（LPS）挑战了暴露于香烟烟雾（CS）的小鼠，然后用 STS 治疗这些小鼠。我们发现 STS 显著改善了 LPS 攻击 CS 暴露小鼠的肺部炎症反应、黏液高分泌和肺功能下降。STS 治疗还显著减弱了 LPS 攻击用香烟烟雾提取物（CSE）处理的人支气管上皮细胞（16HBE）中 IL-6 和 IL-8 的释放增加。从机制上讲，STS 减少了 CS 暴露小鼠肺部和 LPS 攻击用 CSE 处理的 16HBE 细胞中 ERK1/2 和 NF-κB 的激活。总之，STS 可预防 CS 诱导的肺损伤的急性恶化，为阻止 COPD 的急性恶化提供了一种有前途的潜在治疗途径。
