The Protective Of Livdrogen On Lps-induced Acute Lung Injury And Its Underlying Mechanism

The acute lung injury was defined as acute and progressive respiratory failure whichwas caused by factors inside and outside the lung.ALI has become the leading cause ofdeath for patients with severe trauma, extensive burns or severe infection. The majorpathological changes ofALI include impaired gas exchange, neutrophils accumulation,increased vascular permeability and parenchyma injury. Free radicals are considered to bethe final causative molecules in the pathogenesis of lipopolysaccharide (LPS)-induced ALI.Increased production of free radicals combined with decreased antioxidant capacity ofpulmonary vascular tissue contributes to the prognosis ofALI. Treatment with antioxidantssuch as N-acetylcysteine (NAC), edaravone and Vc has been proved to be effective inameliorating the LPS-induced ALI. Hydrogen is a novel energy source and recent attentionhas been focused on it as an energy storage medium with less air pollution when burned. Inthe field of biological medicine, hydrogen has been considered as a physiologically inertgas whose current application was limited in diving medicine. In2007, Ohsawa et al.discovered hydrogen’s ability of selectively reducing hydroxyl radical (.OH) andperoxynitrite (ONOO–). Since then, hydrogen rapidly arouses attraction in the field ofmedical research and has been proved to be an effective treatment measures for manyanimal disease models including acute liver injury, ischemia-reperfusion, acute pancreatitis,Organ transplantation et al, to our knowledge, hydrogen gas has not been tested in theLPS-induced ALI. Endotoxin is thought to be the most important pathogen that leads to the developmentofALI. LPS, endotoxin, derived from the cell wall of gram-negative bacteria, is knownto induce the release of free radicals, overproduction of inflammatory mediators,infiltration of inflammatory cells and tissue edema. In our present study, we producedthe acute lung injury model by intratracheal injection of LPS (5mg/kg body weight) andusing the2%hydrogen inhalation to investigate the protective of hydrogen onLPS-induced acute lung injury and its underlying mechanism. Our research was dividedinto two parts.Part1: Hydrogen attenuated Histopathological alterations including accumulation of alarge number of neutrophils in the intra-and inter-alveolar, alveolar wall thickened, lessalveolar space, interstitial congestion and edema. Our experiments exhibited that adecrease in lung W/D ratio and total protein concentrations in the Broncho AlveolarLavage Fluid (BALF). In addition, hydrogen decreased malonaldehyde (MDA) and3-nitrotyrosine (3-NT) content, inhibited myeloperoxidase (MPO) and maintainedsuperoxide dismutase (SOD) activity in lung tissues and associated with a decrease inthe expression of Tumor necrosis factor (TNF)-α, Interleukin(IL)-1β, IL-6. Hydrogenmitigated LPS-induced lung cell apoptosis. More importantly, hydrogen improved thesurvival rate of mice.Part2: Hydrogen inhibited the activation of P-JNK and Caspase-3. Moreover, theover-expression of Bax and the decreased expression of Bcl-xl were also blocked byhydrogen treatment.In conclusion, our data demonstrated that hydrogen inhalation ameliorated LPS-induced ALI and it may be exerting its protective role by preventing the activation ofROS-JNK-caspase-3pathway...