Department of Infection Control, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China.
Biosci Rep. 2020 Jan 31;40(1). doi: 10.1042/BSR20193667.
We aimed to investigate the regulatory mechanism of lentivirus-mediated overexpression of cystic fibrosis transmembrane conductance regulator (CFTR) in oxidative stress injury and inflammatory response in the lung tissue of mouse model of chronic obstructive pulmonary disease (COPD). COPD mouse model induced by cigarette smoke was established and normal mice were used as control. The mice were assigned into a normal group (control), a model group (untreated), an oe-CFTR group (injection of lentivirus overexpressing CFTR), and an oe-NC group (negative control, injection of lentivirus expressing irrelevant sequences). Compared with the oe-NC group, the oe-CFTR group had higher CFTR expression and a better recovery of pulmonary function. CFTR overexpression could inhibit the pulmonary endothelial cell apoptosis, reduce the levels of glutathione (GSH), reactive oxygen species (ROS), and malondialdehyde (MDA) and increase the values of superoxide dismutase (SOD), GSH peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). The overexpression also led to reductions in the white blood cell (WBC) count in alveolus pulmonis, the concentrations of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor-α, and the protein expressions of NF-κB p65, ERK, JNK, p-EPK, and p-JNK related to MAPK/NF-κB p65 signaling pathway. In conclusion, CFTR overexpression can protect lung tissues from injuries caused by oxidative stress and inflammatory response in COPD mouse model. The mechanism behind this may be related to the suppression of MAPK/NF-κB p65 signaling pathway.
研究慢病毒介导的囊性纤维化跨膜电导调节因子（CFTR）过表达对慢性阻塞性肺疾病（COPD）小鼠模型肺组织氧化应激损伤和炎症反应的调控机制。
采用香烟烟雾诱导 COPD 小鼠模型，以正常小鼠作为对照。将小鼠分为正常组（对照组）、模型组（未处理）、oe-CFTR 组（过表达 CFTR 的慢病毒注射）和 oe-NC 组（阴性对照，注射表达无关序列的慢病毒）。
与 oe-NC 组相比，oe-CFTR 组 CFTR 表达更高，肺功能恢复更好。CFTR 过表达可抑制肺内皮细胞凋亡，降低谷胱甘肽（GSH）、活性氧（ROS）和丙二醛（MDA）水平，增加超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和总抗氧化能力（T-AOC）水平。过表达还导致肺泡白细胞计数、C 反应蛋白（CRP）、白细胞介素（IL）-6 和肿瘤坏死因子-α浓度以及 MAPK/NF-κB p65 信号通路相关蛋白 NF-κB p65、ERK、JNK、p-EPK 和 p-JNK 的降低。
CFTR 过表达可保护 COPD 小鼠模型肺组织免受氧化应激和炎症反应引起的损伤。其机制可能与抑制 MAPK/NF-κB p65 信号通路有关。
