Intensive Care Unit, the First Hospital of Jilin University, Changchun, China.
Department of Nutrition, the Second Hospital of Jilin University, Changchun, China.
PLoS One. 2018 Apr 25;13(4):e0196405. doi: 10.1371/journal.pone.0196405. eCollection 2018.
A major feature of acute lung injury (ALI) is excessive inflammation in the lung. Vitexin is an active component from medicinal plants which has antioxidant and anti-inflammatory activities. Oxidative stress and inflammation play important roles in the pathophysiological processes in ALI. In the current study, we investigate the effect and potential mechanisms of Vitexin on lipopolysaccharide (LPS)-induced ALI.
ALI was induced by LPS intratracheal instillation in C57BL/6 wild-type mice and Nrf2 gene knocked down (Nrf2-/-) mice. One hour before LPS challenge, Vitexin or vehicle intraperitoneal injection was performed. Bronchoalveolar lavage fluid and lung tissues were examined for lung inflammation and injury at 24 h after LPS challenge.
Our animal study's results showed that LPS-induced recruitment of neutrophils and elevation of proinflammatory cytokine levels were attenuated by Vitexin treatment. Vitexin decreased lung edema and alveolar protein content. Moreover, Vitexin activated nuclear factor erythroid-2-related factor 2 (Nrf2), and increased the activity of its target gene heme oxygenase (HO)-1. The LPS-induced reactive oxygen species were inhibited by Vitexin. In addition, the activation of the nucleotide-binding domain and leucine-rich repeat PYD-containing protein 3 (NLRP3) inflammasome was suppressed by Vitexin. However, these effects of Vitexin were abolished in the Nrf2-/- mice. Our cell studies showed that Vitexin enhanced the expression of Nrf2 and HO-1 activity. Moreover, reactive oxygen species (ROS) and IL-1β productions were reduced in Vitexin-treated cells. However, knockdown of Nrf2 by siRNA in RAW cells reversed the benefit of Vitexin.
Vitexin suppresses LPS-induced ALI by controlling Nrf2 pathway.
急性肺损伤（ALI）的一个主要特征是肺部过度炎症。牡荆素是一种来自药用植物的活性成分，具有抗氧化和抗炎作用。氧化应激和炎症在 ALI 的病理生理过程中发挥重要作用。在本研究中，我们研究了牡荆素对脂多糖（LPS）诱导的 ALI 的作用及其潜在机制。
通过 LPS 气管内滴注诱导 C57BL/6 野生型小鼠和 Nrf2 基因敲除（Nrf2-/-）小鼠的 ALI。在 LPS 攻击前 1 小时，腹腔内注射牡荆素或载体。在 LPS 攻击后 24 小时，检查支气管肺泡灌洗液和肺组织，以评估肺炎症和损伤。
我们的动物研究结果表明，牡荆素治疗可减轻 LPS 诱导的中性粒细胞募集和促炎细胞因子水平升高。牡荆素降低了肺水肿和肺泡蛋白含量。此外，牡荆素激活核因子红细胞 2 相关因子 2（Nrf2），增加其靶基因血红素加氧酶（HO）-1 的活性。牡荆素抑制了 LPS 诱导的活性氧。此外，牡荆素抑制核苷酸结合域和富含亮氨酸重复 PYD 结构域包含蛋白 3（NLRP3）炎性小体的激活。然而，在 Nrf2-/-小鼠中，牡荆素的这些作用被消除。我们的细胞研究表明，牡荆素增强了 Nrf2 的表达和 HO-1 活性。此外，牡荆素处理的细胞中活性氧（ROS）和 IL-1β的产生减少。然而，RAW 细胞中 Nrf2 的 siRNA 敲低逆转了牡荆素的益处。
牡荆素通过控制 Nrf2 通路抑制 LPS 诱导的 ALI。
