Aucubin 通过激活 Nrf2/HO-1 信号通路减轻慢性阻塞性肺疾病。
Aucubin Alleviates Chronic Obstructive Pulmonary Disease by Activating Nrf2/HO-1 Signaling Pathway.
发表日期:2024 Jul 05
作者:
Ting Liu, Yang Li, Nan Hu
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
慢性阻塞性肺疾病(COPD)是一种常见的慢性呼吸系统疾病,死亡率较高。 Aucubin 是从杜仲中提取的环烯醚萜苷,在人类疾病中具有抗氧化和抗炎特性。本研究旨在探讨其在COPD小鼠和细胞模型中的具体功能。通过将小鼠长期暴露于香烟烟雾(CS)来建立COPD小鼠模型。测定CS暴露小鼠支气管肺泡灌洗液(BALF)中炎性细胞数及炎性因子肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-8的含量。评估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。 Masson 染色和苏木精-伊红 (H
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.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.