To investigate the protective effects of
penehyclidine hydrochloride (PHC) in
lipopolysaccharide (LPS)-induced
acute lung injury (ALI) and the underlying molecular mechanism. ALI was induced by
intravenous injection of LPS (5mg/kg). Male Sprague-Dawley (SD) rats challenged with or without LPS were pretreated with varied doses of PHC 0.5h before injection of LPS or saline. Blood gas in arterial blood, lung
weight gain, bronchoalveolar lavage fluid (BALF), and neutrophils sequestration were examined 6h after administration of LPS. Pathological changes of lung tissue were measured by light microscopy. Phosphorylation of
mitogen-activated protein kinase (MAPK) family and
NF-kappaB were detected by western blot. All animals demonstrated drops in arterial
oxygen tension (PaO(2)) after LPS application, which were significantly reversed by PHC pretreatment. Administration of PHC reduced lung water gain, bronchoalveolar lavage
protein content, infiltration of neutrophils,
malondialdehyde (MDA) content, and
lactate dehydrogenase (LDH) activity and enhanced
superoxide dismutase (SOD) activity. Histopathological study also indicated that PHC treatment markedly attenuated lung histopathological changes, alveolar
hemorrhage, and inflammatory cells infiltration with evidence of decreasing of
myeloperoxidase (MPO) activity. Furthermore, p38MAPK, ERK, and
NF-kappaB were activated in 6h after LPS treatment, which could be blunted by PHC, while JNK remained unchanged. These findings confirmed significant protection by PHC against LPS-induced lung vascular leak and
inflammation and implicated inhibition of p38MAPK activation signaling a potential role for PHC in the management of ALI.