Department of International Medical Center, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Cell Biochem Biophys. 2024 Sep;82(3):2439-2454. doi: 10.1007/s12013-024-01354-1. Epub 2024 Jul 5.
Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with high death rates. Aucubin is an iridoid glycoside extracted from Eucommia ulmoides with antioxidative and anti-inflammatory properties in human diseases. This study aimed to investigate its specific function in mouse and cell models of COPD.
The COPD mouse model was established by exposing mice to a long-term cigarette smoke (CS). The number of inflammatory cells and the contents of inflammatory factors tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-8 in bronchoalveolar lavage fluid (BALF) of CS-exposed mice were measured. The levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) in the lung tissues were estimated. Masson staining and hematoxylin-eosin (H&E) staining were utilized to evaluate pulmonary fibrosis and emphysema in CS-treated mice. Cell apoptosis in the lung tissues was estimated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Western blot was applied to quantify protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and apoptotic markers. COPD cell model was established by exposing mouse lung epithelial cells (MLE12) with cigarette smoke extract to further verify the properties of aucubin in vitro.
Aucubin reduced the number of inflammatory cells and decreased the contents of TNF-α, IL-6, and IL-8 in BALF of CS-treated mice. The oxidative stress, lung emphysema, fibrosis, and lung cell apoptosis induced by CS exposure were ameliorated by aucubin administration. Aucubin activated the Nrf2/HO-1 signaling pathway in vitro and in vivo. Pretreatment with ML385, a specific Nrf2 inhibitor, antagonized the protective effects of aucubin on inflammation, oxidative stress, fibrosis, and cell apoptosis in COPD.
Aucubin alleviates inflammation, oxidative stress, apoptosis, and pulmonary fibrosis in COPD mice and CSE-treated MLE12 cells by activating the Nrf2/HO-1 signaling pathway.
慢性阻塞性肺疾病（COPD）是一种常见的慢性呼吸道疾病，死亡率较高。梓醇是从杜仲中提取的环烯醚萜苷，具有抗氧化和抗炎作用。本研究旨在探讨其在 COPD 小鼠和细胞模型中的特定作用。
通过长期暴露于香烟烟雾（CS）建立 COPD 小鼠模型。测量 CS 暴露小鼠支气管肺泡灌洗液（BALF）中炎症细胞数量和炎症因子肿瘤坏死因子-α（TNF-α）、白细胞介素 6（IL-6）和白细胞介素 8（IL-8）的含量。估计肺组织中超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、丙二醛（MDA）和髓过氧化物酶（MPO）的水平。采用 Masson 染色和苏木精-伊红（H&E）染色评估 CS 处理小鼠的肺纤维化和肺气肿。通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）测定评估肺组织中的细胞凋亡。Western blot 用于定量核因子红细胞 2 相关因子 2（Nrf2）、血红素加氧酶-1（HO-1）和凋亡标志物的蛋白水平。通过用香烟烟雾提取物暴露小鼠肺上皮细胞（MLE12）建立 COPD 细胞模型，进一步验证梓醇的性质。
梓醇减少了 CS 处理小鼠 BALF 中的炎症细胞数量，并降低了 TNF-α、IL-6 和 IL-8 的含量。梓醇减轻了 CS 暴露引起的氧化应激、肺肺气肿、纤维化和肺细胞凋亡。梓醇在体外和体内激活了 Nrf2/HO-1 信号通路。用特异性 Nrf2 抑制剂 ML385 预处理拮抗了梓醇对 COPD 炎症、氧化应激、纤维化和细胞凋亡的保护作用。
梓醇通过激活 Nrf2/HO-1 信号通路，减轻 COPD 小鼠和 CSE 处理的 MLE12 细胞中的炎症、氧化应激、凋亡和肺纤维化。
