Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
Department of Physiology, School of Medicine, Tzu Chi University, Hualien, Taiwan.
Respir Physiol Neurobiol. 2022 Jan;295:103787. doi: 10.1016/j.resp.2021.103787. Epub 2021 Sep 17.
This study investigated whether intermittent hypoxia (IH) induces airway hyperresponsiveness (AHR) and associated with lung inflammation. Male Brown Norway rats were exposed to 14-day IH or room air (RA) for 6 h/day. One day after the last exposure, total lung resistance to various doses of methacholine was measured as an index of bronchoconstrictive responses. Compared with RA controls, methacholine significantly induced an augmented bronchoconstriction in IH-exposed rats. Moreover, IH exposure evoked lung inflammation which was reflected by increased inflammatory cell infiltration, concentrations of interleukin-6 and prostaglandin E in bronchoalveolar lavage fluid, and lung lipid peroxidation. IH-induced AHR and lung inflammation were completely abolished by daily intraperitoneal injection of N-acetylcysteine (an antioxidant) or ibuprofen (a cyclooxygenase inhibitor), but not by apocynin (an inhibitor of NADPH oxidase) or vehicle. In conclusion, AHR and lung inflammation occur after 14-day IH exposure, with endogenous reactive oxygen species and cyclooxygenase metabolites being responsible for these responses.
这项研究旨在探讨间歇性低氧（IH）是否会引起气道高反应性（AHR），并伴有肺部炎症。雄性棕色挪威大鼠接受 14 天的 IH 或室内空气（RA）暴露，每天 6 小时。最后一次暴露后一天，通过测量各种剂量的乙酰甲胆碱引起的总肺阻力来评估支气管收缩反应。与 RA 对照组相比，IH 暴露组的乙酰甲胆碱明显引起更严重的支气管收缩。此外，IH 暴露会引起肺部炎症，这反映在支气管肺泡灌洗液中炎症细胞浸润增加、白细胞介素-6 和前列腺素 E 的浓度增加以及肺脂质过氧化增加。每日腹腔注射 N-乙酰半胱氨酸（一种抗氧化剂）或布洛芬（一种环氧化酶抑制剂）可完全消除 IH 诱导的 AHR 和肺炎症，但不能消除 apocynin（一种 NADPH 氧化酶抑制剂）或载体。总之，14 天的 IH 暴露后会发生 AHR 和肺炎症，内源性活性氧和环氧化酶代谢物是这些反应的原因。
