Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Life Sci. 2018 Oct 1;210:86-95. doi: 10.1016/j.lfs.2018.08.064. Epub 2018 Aug 29.
Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia with diffuse alveolar damage and increased pulmonary microvascular permeability. Honokiol (HKL), the principal active ingredient of Chinese herb magnolia officinalis, protected the lung of experimental ARDS models via attenuation of inflammation and oxidative stress. However, whether HKL has protective effects against the dysfunction of pulmonary microvascular endothelial barrier and the potential mechanisms remain unclear.
In the present study, we examined the levels of plasma Angiopoietin-2 (Ang-2) in ARDS patients, explored the effects of HKL on the vascular endothelial barrier at the ARDS animal and cell levels.
Our data showed that compared with the healthy controls, circulating Ang-2 level was higher in the patients with ARDS, and were usually supposed to be positively related to the severity of ARDS. Moreover, HKL effectively inhibited lung inflammatory injury and microvascular leakage, and improved ARDS mice survival. HKL also inhibited the expression of Ang-2, ICAM-1 and VCAM-1, and restored the expression of Sirt3, β-Catenin and VE-Cadherin. Furthermore, HKL improved ECs survival and inhibited the apoptosis of ECs. The inhibition of Ang-2 expression in vitro by HKL is accompanied by the upregulation of Sirt3 and AMPK phosphorylation.
Our data demonstrated that HKL protected pulmonary microvascular endothelial barrier against LPS-induced ARDS at least in part through activating the Sirt3/AMPK signaling and inhibiting the Ang-2 expression. Thus, our findings show that the activation of Sirt3 signaling is a potential mechanism for the protective effects of HKL on vascular barrier.
急性呼吸窘迫综合征（ARDS）的特征是急性低氧血症伴弥漫性肺泡损伤和肺微血管通透性增加。厚朴酚（HKL）是中药厚朴的主要活性成分，通过减轻炎症和氧化应激，对实验性 ARDS 模型的肺具有保护作用。然而，HKL 是否对肺微血管内皮屏障功能障碍具有保护作用及其潜在机制尚不清楚。
在本研究中，我们检测了 ARDS 患者血浆血管生成素-2（Ang-2）的水平，探讨了 HKL 在 ARDS 动物和细胞水平对血管内皮屏障的影响。
我们的数据显示，与健康对照组相比，ARDS 患者的循环 Ang-2 水平较高，通常与 ARDS 的严重程度呈正相关。此外，HKL 能有效抑制肺炎症损伤和微血管渗漏，并提高 ARDS 小鼠的存活率。HKL 还抑制 Ang-2、ICAM-1 和 VCAM-1 的表达，并恢复 Sirt3、β-Catenin 和 VE-Cadherin 的表达。此外，HKL 还能改善内皮细胞的存活并抑制内皮细胞的凋亡。HKL 在体外抑制 Ang-2 表达的同时，还能上调 Sirt3 和 AMPK 磷酸化。
我们的数据表明，HKL 通过激活 Sirt3/AMPK 信号通路和抑制 Ang-2 表达，保护肺微血管内皮屏障免受 LPS 诱导的 ARDS。因此，我们的研究结果表明，Sirt3 信号的激活是 HKL 对血管屏障保护作用的潜在机制之一。
