College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, Daegu, 41566, Republic of Korea.
Department of Biochemistry, College of Medicine, Gachon University, Incheon, 21999, Republic of Korea.
Environ Res. 2020 Apr;183:109230. doi: 10.1016/j.envres.2020.109230. Epub 2020 Feb 5.
Particulate matter (PM), the collection of all liquid and solid particles suspended in air, includes both organic and inorganic particles, many of which are health-hazards. PM particles with a diameter equal to or less than 2.5 μm (PM) is a form of air pollutant that causes significant lung damage when inhaled. Maslinic acid (MA) prevents oxidative stress and pro-inflammatory cytokine generation, but there is little information available regarding its role in PM-induced lung injury. Therefore, the purpose of this study was to determine the protective activity of MA against PM-induced lung injury. The mice were divided into seven groups (n = 10 each): a mock control group, an MA control (0.8 mg/kg mouse body weight) group, an opted PM produced from diesel (10 mg/kg mouse body weight) group, a diesel PM+MA (0.2, 0.4, 0.6, and 0.8 mg/kg mouse body weight) groups. Mice were treated with MA via tail-vein injection 30 min after the intratracheal instillation of a diesel PM. Changes in the wet/dry weight ratio of the lung tissue, total protein/total cell and lymphocyte counts, inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), vascular permeability, and histology were monitored in diesel PM-treated mice. The results showed that MA reduced pathological lung injury, the wet/dry weight ratio of the lung tissue, and hyperpermeability caused by diesel PM. MA also inhibited diesel PM-induced myeloperoxidase (MPO) activity in the lung tissue, decreased the levels of diesel PM-induced inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, reduced nitric oxide (NO) and total protein in the BALF, and effectively attenuated diesel PM-induced increases in the number of lymphocytes in the BALF. In addition, MA increased the protein phosphorylation of the mammalian target of rapamycin (mTOR) and dramatically suppressed diesel PM-stimulated expression of toll-like receptor 4 (TLR4), MyD88, and the autophagy-related proteins LC3 II and Beclin 1. In conclusion, these findings indicate that MA has a critical anti-inflammatory effect due to its ability to regulate both the TLR4-MyD88 and mTOR-autophagy pathways and may thus be a potential therapeutic agent against diesel PM-induced lung injury.
颗粒物 (PM) 是指悬浮在空气中的所有液体和固体颗粒的集合，包括有机和无机颗粒，其中许多颗粒对健康有害。直径等于或小于 2.5μm 的 PM 颗粒是一种空气污染物，吸入时会对肺部造成严重损害。齐墩果酸 (MA) 可防止氧化应激和促炎细胞因子的产生，但关于其在 PM 诱导的肺损伤中的作用的信息很少。因此，本研究旨在确定 MA 对 PM 诱导的肺损伤的保护作用。将小鼠分为七组（每组 10 只）：模拟对照组、MA 对照组（0.8mg/kg 小鼠体重）、柴油产生的 PM 组（10mg/kg 小鼠体重）、柴油 PM+MA 组（0.2、0.4、0.6 和 0.8mg/kg 小鼠体重）。在气管内滴注柴油 PM 30 分钟后，通过尾静脉注射 MA 对小鼠进行处理。监测柴油 PM 处理小鼠的肺组织湿/干重比、总蛋白/总细胞和淋巴细胞计数、支气管肺泡灌洗液 (BALF) 中的炎症细胞因子、血管通透性和组织学变化。结果表明，MA 减轻了 PM 引起的肺组织病理学损伤、湿/干重比和高通透性。MA 还抑制了肺组织中柴油 PM 诱导的髓过氧化物酶 (MPO) 活性，降低了 TNF-α 和 IL-1β 等炎症细胞因子的水平，降低了 BALF 中的一氧化氮 (NO) 和总蛋白含量，并有效减轻了 BALF 中淋巴细胞数量的增加。此外，MA 增加了雷帕霉素靶蛋白 (mTOR) 的蛋白磷酸化，并显著抑制了 TLR4、MyD88 和自噬相关蛋白 LC3 II 和 Beclin 1 表达。总之，这些发现表明，MA 具有关键的抗炎作用，因为它能够调节 TLR4-MyD88 和 mTOR-自噬途径，因此可能是治疗柴油 PM 诱导的肺损伤的潜在治疗剂。
