title: Treatment of low molecular weight heparin inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats.
abstract: To determine whether low molecular weight heparin (LMWH) is able to reduce pulmonary inflammation and improve the survival in rats with endotoxin-induced acute lung injury (ALI). Rat ALI model was reproduced by injection of lipopolysaccharide (LPS) into tail vein. Rats were divided randomly into three groups: control group, ALI group, LMWH-treated group. Blood was collected and lung tissue was harvested at the designated time points for analysis. The lung specimens were harvested for morphological studies, streptavidin-peroxidase immunohistochemistry examination. Lung tissue edema was evaluated by tissue water content. The levels of lung tissue myeloperoxidase (MPO) were determined. Meanwhile, the nuclear factor-kappa B (NF-κB) activation, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels and high mobility group box 1 (HMGB1) and intercellular adhesion molecule-1 (ICAM-1) protein levels in the lung were studied. In survival studies, a separate group of rats were treated with LMWH or sterile saline after LPS administration. Then, the mortality was recorded. Treatment with LMWH after ALI was associated with a reduction in the severity of LPS-induced lung injury. Treatment with LMWH significantly decreased the expression of TNF-α, IL-1β, HMGB1 and ICAM-1 in the lung of ALI rats. Similarly, treatment with LMWH dramatically diminished LPS-induced neutrophil sequestration and markedly reduced the enhanced lung permeability. In the present study, LMWH administration inhibited the nuclear translocation of NF-κB in the lung. Survival was significantly higher among the LMWH-treated group compared with the ALI group. These data suggest that LMWH attenuates inflammation and prevents lethality in endotoxemic rats.
authors.affiliation: Department of Intensive Care Unit, The First Hospital of China Medical University, 155 Nanjing North Street, Shenyang, 110001, Liaoning Province, China, zgl17698@sina.com.
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Luan
authors.forename: Mendsaikhan
authors.initials: M
authors.lastname: Naranpurev
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Ma
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D055371:Acute Lung Injury / Q000188:drug therapy* / Q000517:prevention & control; D000818:Animals; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy* / Q000473:pathology; D019446:Endotoxemia / Q000188:drug therapy* / Q000401:mortality; D004731:Endotoxins / Q000276:immunology / Q000633:toxicity*; D024243:HMGB1 Protein / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D004731:Endotoxins; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D006495:Heparin, Low-Molecular-Weight; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D052002:NF-kappa B p50 Subunit; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase