title: Low molecular weight heparin may prevent acute lung injury induced by sepsis in rats.
abstract: The purpose of this study was to assess the protective effect of low molecular weight heparin (LMWH) on acute lung injury (ALI) in rats induced by sepsis. Rat ALI model was reproduced by cecal ligation and puncture (CLP). All rats were randomly divided into three groups (n=50): control group (A), ALI group (B), and LMWH-treated group (C). Group A received a sham operation and the other groups underwent CLP operation. Groups A and B accepted intraperitoneal injection (i.p.) of normal saline (NS) at a dose of 2.0 ml kg(-1) and ceftriaxone (30 mg kg(-1)), group C was intraperitoneally injected with additional LMWH (150 U kg(-1)) except saline and ceftriaxone. Blood was collected and lung tissue was harvested at the designated time points for analysis. The lung specimens were harvested for morphological studies, 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, high mobility group box 1 (HMGB1) and intercellular adhesion molecule-1 (ICAM-1) protein levels in the lung were studied. There was a significant difference in each index between groups A and B (P<0.05). Treatment with LMWH significantly decreased the expression of TNF-α, IL-1β, HMGB1 and ICAM-1 in the lungs of ALI rats. Similarly, treatment with LMWH dramatically diminished sepsis-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 lungs. These data suggest that LMWH attenuates inflammation and ameliorates lung pathology in CLP-induced sepsis in a rat model.
authors.affiliation: Department of Critical Care Medicine, Qilu Hospital, Shandong University, 107# Wenhua Xi Road, Jinan 250012, PR China; Department of Critical Care Medicine, The Affiliated Hospital of Binzhou Medical University, Binzhou 256603, PR China.
authors.forename: Fangyu
authors.initials: F
authors.lastname: Ning
authors.affiliation: Department of Critical Care Medicine, The Affiliated Hospital of Binzhou Medical University, Binzhou 256603, PR China.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, Yantai Affiliated Hospital of Binzhou Medical University, YanTai, ShanDong 264003, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Shang
authors.affiliation: Department of Critical Care Medicine, The Affiliated Hospital of Binzhou Medical University, Binzhou 256603, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, The Affiliated Hospital of Binzhou Medical University, Binzhou 256603, PR China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Critical Care Medicine, The Affiliated Hospital of Binzhou Medical University, Binzhou 256603, PR China.
authors.forename: Zhijiang
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Critical Care Medicine, Qilu Hospital, Shandong University, 107# Wenhua Xi Road, Jinan 250012, PR China. Electronic address: wdw.55@163.com.
authors.forename: Dawei
authors.initials: D
authors.lastname: Wu
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000517:prevention & control*; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000096:biosynthesis; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008168:Lung / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D024243:HMGB1 Protein; D006495:Heparin, Low-Molecular-Weight; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002443:Ceftriaxone; D009195:Peroxidase
keywords: Low molecular weight heparin; Lung injury; Sepsis