Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
Pulm Pharmacol Ther. 2021 Jun;68:102018. doi: 10.1016/j.pupt.2021.102018. Epub 2021 Mar 24.
Acute lung injury (ALI) remains a serious challenge in the intensive care unit. Inflammation plays a key role in the progression of ALI. Chrysin (CHR) is a natural flavonoid with anti-inflammatory functions. We investigated the anti-inflammatory effects in a mouse model of ALI induced by lipopolysaccharide (LPS), and identified the underlying mechanisms of its action. Following CHR administration, mice were challenged with LPS intratracheally for 6 h to induce ALI. Compared to mice challenged with LPS alone, the presence of CHR showed a reduction in the development of lung injuries, as confirmed by histopathological observation. Pre-treatment with CHR attenuated inflammation by reducing the production of myeloperosidase (MPO), and pro-inflammatory cytokine levels in the lung and bronchoalveolar lavage fluid (BALF). Furthermore, CHR improved lung edema by reducing the vascular permeability, as demonstrated by less evans blue staining in the lung tissue and low levels of protein in BALF. In addition, our results proved that CHR improved the antioxidant capacity by increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the lung tissue. Results of western blot assays suggested that CHR suppressed the LPS-induced expression of glucose-regulated protein 78 (GRP78) and phosphorylated inositol-requiring enzyme 1α (p-IRE1α). We also found that CHR suppressed the expression of thioredoxin interaction protein (TXNIP), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and cleaved caspase-1. In conclusion, CHR improved vascular permeability and mitigated the inflammatory response of lung tissue by suppressing the IRE1α/TXNIP/NLRP3 pathway, thereby alleviating LPS-induced ALI in the lungs of mice.
急性肺损伤（ALI）仍然是重症监护病房的一个严重挑战。炎症在 ALI 的进展中起着关键作用。白杨素（CHR）是一种具有抗炎功能的天然黄酮类化合物。我们研究了 CHR 在脂多糖（LPS）诱导的 ALI 小鼠模型中的抗炎作用，并确定了其作用的潜在机制。CHR 给药后，用 LPS 经气管内滴注 6 小时诱导 ALI。与单独用 LPS 处理的小鼠相比，CHR 的存在显示出肺损伤的发展减少，这通过组织病理学观察得到证实。CHR 通过减少髓过氧化物酶（MPO）的产生和肺及支气管肺泡灌洗液（BALF）中促炎细胞因子的水平来减轻炎症。此外，CHR 通过减少肺组织中伊文思蓝染色和 BALF 中蛋白水平来减轻肺水肿，从而改善肺水肿。此外，我们的结果证明 CHR 通过增加肺组织中超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性来提高抗氧化能力。Western blot 分析结果表明，CHR 抑制 LPS 诱导的葡萄糖调节蛋白 78（GRP78）和磷酸肌醇需要酶 1α（p-IRE1α）的表达。我们还发现 CHR 抑制硫氧还蛋白相互作用蛋白（TXNIP）、核苷酸结合寡聚化结构域样受体蛋白 3（NLRP3）和切割的半胱天冬酶-1 的表达。总之，CHR 通过抑制 IRE1α/TXNIP/NLRP3 通路改善了血管通透性并减轻了肺组织的炎症反应，从而减轻了 LPS 诱导的小鼠肺部 ALI。
