Yu Dan, Wang Fan, Ye Shuming, Yang Shuo, Yu Ning, Zhou Xinyan, Zhang Nian
Department of Hematology, Wuhan No. 1 Hospital, Wuhan 43022, Hubei, China.
General Medical Department (Department of Geriatrics), Wuhan No. 1 Hospital, Wuhan 43022, Hubei, China.
Open Med (Wars). 2022 Feb 22;17(1):375-383. doi: 10.1515/med-2022-0416. eCollection 2022.
Chronic obstructive pulmonary disease (COPD) is mainly caused by cigarette smoking (CS), with oxidative stress being one key component during its pathogenesis. This study aimed to investigate the effects of quercitrin (QE) on cigarette smoke extract (CSE)-induced cell apoptosis and oxidative stress in human bronchial epithelial cells (HBECs) and its underlying mechanism. HBECs were treated with 2% CSE for 24 h to establish COPD cellular models. CCK-8 assay and flow cytometry analysis were performed to evaluate cell viability and apoptosis, respectively. Western blotting was applied to examine protein levels and ELISA kits were used to examine contents of the indicated oxidant/antioxidant markers. The results demonstrated that CSE promoted apoptosis and suppressed viability of HBECs and QE reversed these effects. CSE caused increase in T-AOC, superoxide dismutase, and glutathione (GSH) peroxidase contents and decrease in MDA, reactive oxygen species , and GSH contents in HBECs, which were rescued by QE treatment. The CSE-induced Nrf2 nuclear translocation and elevation of NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) expression were also reversed by QE in HBECs. The mitogen-activated protein kinase (MAPK) signaling was activated by CSE and further suppressed by QE in HBECs. Collectively, QE exerts a protective role in HBECs against cell apoptosis and oxidative damage via inactivation of the Nrf2/HO-1/NQO1 pathway and the MAPK/ERK pathway.
慢性阻塞性肺疾病（COPD）主要由吸烟（CS）引起，氧化应激是其发病机制中的一个关键因素。本研究旨在探讨槲皮苷（QE）对香烟烟雾提取物（CSE）诱导的人支气管上皮细胞（HBECs）细胞凋亡和氧化应激的影响及其潜在机制。用2% CSE处理HBECs 24小时以建立COPD细胞模型。分别进行CCK-8测定和流式细胞术分析以评估细胞活力和凋亡。采用蛋白质印迹法检测蛋白质水平，并用ELISA试剂盒检测所示氧化/抗氧化标志物的含量。结果表明，CSE促进HBECs凋亡并抑制其活力，而QE可逆转这些作用。CSE导致HBECs中总抗氧化能力（T-AOC）、超氧化物歧化酶和谷胱甘肽（GSH）过氧化物酶含量增加，丙二醛、活性氧（ROS）和GSH含量降低，而QE处理可使其恢复。CSE诱导的Nrf2核转位以及NAD（P）H：醌氧化还原酶1（NQO1）和血红素加氧酶-1（HO-1）表达的升高也被HBECs中的QE逆转。丝裂原活化蛋白激酶（MAPK）信号在HBECs中被CSE激活并被QE进一步抑制。总体而言，QE通过使Nrf2/HO-1/NQO1途径和MAPK/ERK途径失活，对HBECs发挥抗细胞凋亡和氧化损伤的保护作用。
