title: Sodium Hydrosulphide alleviates remote lung injury following limb traumatic injury in rats.
abstract: Hydrogen sulphide (H2S) was found to attenuate ventilator or oleic acid induced lung injury. The aim of this study was to explore the effects of exogenous H2S donor, sodium Hydrosulphide (NaHS), on lung injury following blast limb trauma and the underlying mechanisms. For in vitro experiments, pulmonary micro-vessel endothelial cells (PMVECs) were cultured and treated with NaHS or vehicle in the presence of TNF-α. For in vivo, blast limb traumatic rats, induced by using chartaceous electricity detonators, were randomly treated with NaHS, cystathionine gamma-lyase inhibitor (PAG) or vehicle. In vitro, NaHS (100 µM) treatment increased PMVECs viability and decreased LDH release into culture media after tumor necrosis factor (TNF) α challenge. In addition, NaHS treatment prevented the increase of nitric oxide, Intercellular Adhesion Molecule 1(ICAM-1) and interleukin (IL)-6 production and inducible nitric oxide synthase activation induced by TNF-α. Knock-down of NF-E2-Related Factor 2 (Nrf2) partially abolished the protective effect of NaHS. In vivo, NaHS treatment significantly alleviated lung injury following blast limb trauma, demonstrated by a decreased histopathological score and lung water content. Furthermore, NaHS treatment reversed the decrease of H2S concentration in plasma, prevented the increase of TNF-α, IL-6, malondialdehyde and myeloperoxidase, increased the Nrf2 downstream effector glutathione in both plasma and lungs, and reversed the decrease of superoxide dismutase in both plasma and lungs induced by blast limb trauma. Our data indicated that NaHS protects against lung injury following blast limb trauma which is likely associated with suppression of the inflammatory and oxidative response and activation of Nrf2 cellular signal.
authors.affiliation: Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jiaolin
authors.initials: J
authors.lastname: Ning
authors.forename: Liwen
authors.initials: L
authors.lastname: Mo
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Zhao
authors.forename: Kaizhi
authors.initials: K
authors.lastname: Lu
authors.forename: Xinan
authors.initials: X
authors.lastname: Lai
authors.forename: Xianghong
authors.initials: X
authors.lastname: Luo
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhao
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005121:Extremities / Q000293:injuries*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D055370:Lung Injury / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D013440:Sulfides / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C025451:sodium bisulfide