Alateeq Rana, Akhtar Alina, De Luca Simone N, Chan Stanley M H, Vlahos Ross
Respiratory Research Group, Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, Melbourne, VIC 3083, Australia.
Antioxidants (Basel). 2024 Jul 16;13(7):855. doi: 10.3390/antiox13070855.
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and is primarily caused by cigarette smoking (CS). Neurocognitive comorbidities such as anxiety and cognitive impairments are common among people with COPD. CS-induced lung inflammation and oxidative stress may "spill-over" into the systemic circulation, driving the onset of these comorbidities. We investigated whether a prophylactic treatment with the NADPH Oxidase 2 (NOX2) inhibitor, apocynin, could prevent CS-induced neurocognitive impairments. Adult male BALB/c mice were exposed to CS (9 cigarettes/day, 5 days/week) or room air (sham) for 8 weeks with co-administration of apocynin (5 mg/kg, intraperitoneal injection once daily) or vehicle (0.01% DMSO in saline). Following 7 weeks of CS exposure, mice underwent behavioral testing to assess recognition and spatial memory (novel object recognition and Y maze, respectively) and anxiety-like behaviors (open field and elevated plus maze). Mice were then euthanized, and blood, lungs, and brains were collected. Apocynin partially improved CS-induced lung neutrophilia and reversed systemic inflammation (C-reactive protein) and oxidative stress (malondialdehyde). Apocynin exerted an anxiolytic effect in CS-exposed mice, which was associated with restored microglial profiles within the amygdala and hippocampus. Thus, targeting oxidative stress using apocynin can alleviate anxiety-like behaviors and could represent a novel strategy for managing COPD-related anxiety disorders.
慢性阻塞性肺疾病（COPD）是全球第三大致死原因，主要由吸烟（CS）引起。神经认知共病如焦虑和认知障碍在COPD患者中很常见。CS诱导的肺部炎症和氧化应激可能“溢出”到体循环中，引发这些共病的发生。我们研究了用NADPH氧化酶2（NOX2）抑制剂阿朴吗啡进行预防性治疗是否能预防CS诱导的神经认知障碍。成年雄性BALB/c小鼠暴露于CS（每天9支香烟，每周5天）或室内空气（假手术组）8周，同时腹腔注射阿朴吗啡（5mg/kg，每日一次）或溶剂（0.01%二甲基亚砜溶于生理盐水）。在暴露于CS 7周后，对小鼠进行行为测试，以评估识别和空间记忆（分别为新物体识别和Y迷宫）以及焦虑样行为（旷场试验和高架十字迷宫）。然后对小鼠实施安乐死，并采集血液、肺和脑。阿朴吗啡部分改善了CS诱导的肺部嗜中性粒细胞增多，并逆转了全身炎症（C反应蛋白）和氧化应激（丙二醛）。阿朴吗啡对暴露于CS的小鼠具有抗焦虑作用，这与杏仁核和海马体内小胶质细胞形态的恢复有关。因此，使用阿朴吗啡靶向氧化应激可以减轻焦虑样行为，可能代表一种治疗COPD相关焦虑症的新策略。
