The α7 nicotinic acetylcholine receptor agonist GTS-21 attenuates hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation

摘要

Systemic administration of GTS-21 decreases lung injury in mice exposed to prolonged hyperoxia. C57BL/6 mice were exposed to either ≥99% O for 3 days or 21% O (room air). Mice were randomized to receive either GTS-21 (0.04, 0.4 and 4 mg/kg) or saline, administrated by intraperitoneal injection every 8 h starting at 32 h following the onset of hyperoxic exposure. Lungs and BAL were harvested at the end of hyperoxia treatment. The total protein content in the BAL was measured as a marker of lung injury. Lungs, harvested at the end of hyperoxic exposure, were fixed, embedded and sectioned. Images of the Hematoxylin-eosin-stain of the lung sections from room air samples (RA), and hyperoxic samples from mice treated with either vehicle saline control (0 m/kg) or GTS-21, (4 mg/kg) are shown ( ) and their lung histopathological scores assessed ( ). Data represent the mean ± SEM from three independent experiments (  = 6–10 mice/group). *