Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China.
Eur J Pharm Sci. 2013 Mar 12;48(4-5):819-24. doi: 10.1016/j.ejps.2012.12.031. Epub 2013 Jan 13.
The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Angiotensin converting enzyme 2 (ACE2) plays a protective role in acute lung injury. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to have anti-inflammatory effect, but the effect of osthole on the ALI is largely unknown. The aim of this study is to explore whether and by what mechanisms osthole protects lipopolysaccharide(LPS)-induced acute lung injury. Herein, we found that osthole had a beneficial effect on LPS-induced ALI in mice. As revealed by survival study, pretreatment with high doses of osthole reduced the mortality of mice from ALI. Osthole pretreatment significantly improved LPS-induced lung pathological changes, reduced lung wet/dry weight ratios and total protein in BALF. Osthole also inhibited the release of inflammatory mediators TNF-α and IL-6. Meanwhile, osthole markedly prevented the loss of ACE2 and Ang1-7 in lung tissue of ALI mice. ACE2 inhibitor blocked the protective effect of osthole in NR 8383 cell lines. Taken together, our study showed that osthole improved survival rate and attenuated LPS-induced ALI and ACE2 may play a role in it.
肾素-血管紧张素-醛固酮系统（RAAS）在急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）的发病机制中起重要作用。血管紧张素转换酶 2（ACE2）在急性肺损伤中起保护作用。蛇床子素是从传统中药中提取的一种天然香豆素衍生物，已知具有抗炎作用，但蛇床子素对 ALI 的作用在很大程度上尚不清楚。本研究旨在探讨蛇床子素是否以及通过何种机制保护脂多糖（LPS）诱导的急性肺损伤。在此，我们发现蛇床子素对 LPS 诱导的小鼠 ALI 具有有益作用。通过生存研究显示，蛇床子素预处理可降低 LPS 诱导的 ALI 小鼠的死亡率。蛇床子素预处理可显著改善 LPS 诱导的肺组织病理变化，降低肺湿/干重比和 BALF 中的总蛋白含量。蛇床子素还抑制了 TNF-α和 IL-6 等炎症介质的释放。同时，蛇床子素明显阻止了 ALI 小鼠肺组织中 ACE2 和 Ang1-7 的丢失。ACE2 抑制剂阻断了蛇床子素在 NR 8383 细胞系中的保护作用。综上所述，我们的研究表明蛇床子素可提高存活率并减轻 LPS 诱导的 ALI，而 ACE2 可能在其中发挥作用。
