Chen Dan, Gao Zhi-Qi, Wang Ying-Ying, Wan Bin-Bin, Liu Gang, Chen Jun-Liang, Wu Ya-Xian, Zhou Qin, Jiang Shan-Yu, Yu Ren-Qiang, Pang Qing-Feng
Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, People's Republic of China.
Department of Neonatology, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu Province, People's Republic of China.
J Inflamm Res. 2021 Mar 10;14:803-816. doi: 10.2147/JIR.S303105. eCollection 2021.
Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms.
WT, Nrf2 mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested.
The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2 neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs.
SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.
肺泡停滞以及慢性炎症和氧化应激引起的血管生成受损是支气管肺发育不良（BPD）的两个主要因素。短链脂肪酸（SCFAs），尤其是丙酸，具有抗氧化和抗炎作用。本研究旨在探讨丙酸钠（SP）对脂多糖（LPS）诱导的BPD的作用及其潜在机制。
本研究使用野生型（WT）、Nrf2基因敲除小鼠和肺微血管内皮细胞（HPMECs）。通过LPS诱导建立体内和体外BPD模型。研究了与BPD发病机制相关的肺组织病理学、炎症和氧化应激相关mRNA表达。此外，还检测了细胞活力和血管生成情况。
在LPS诱导的新生小鼠BPD模型中，SP处理后观察到核因子红细胞2相关因子（Nrf2）表达增加， Kelch样ECH相关蛋白1（Keap-1）表达减少。在LPS诱导的野生型而非Nrf2基因敲除新生小鼠中，SP减轻了肺部炎症和氧化应激，并表现出明显的肺泡病理改变。此外，在LPS刺激的HPMECs中，SP促进了Nrf2核转位，表现出细胞保护和促血管生成作用。此外，SP通过阻断核因子κB通路的激活减轻了LPS诱导的炎症反应。此外，用Nrf2特异性抑制剂ML385预处理可抵消SP对LPS刺激的HPMECs中炎症、氧化应激和血管生成的有益作用。
SP以Nrf2依赖的方式保护新生小鼠和HPMECs免受LPS诱导的肺泡简化和异常血管生成。
