Treatment of low molecular weight heparin inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats

Inflammation. 2014 Jun;37(3):924-32. doi: 10.1007/s10753-014-9812-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / prevention & control
  • Animals
  • Cytokines / blood
  • Disease Models, Animal
  • Edema / drug therapy*
  • Edema / pathology
  • Endotoxemia / drug therapy*
  • Endotoxemia / mortality
  • Endotoxins / immunology
  • Endotoxins / toxicity*
  • HMGB1 Protein / metabolism
  • Heparin, Low-Molecular-Weight / pharmacology*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-1beta / metabolism
  • Lung / pathology
  • Male
  • NF-kappa B p50 Subunit / metabolism
  • Neutrophils / immunology
  • Peroxidase / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Endotoxins
  • HMGB1 Protein
  • Hbp1 protein, rat
  • Heparin, Low-Molecular-Weight
  • IL1B protein, rat
  • Interleukin-1beta
  • NF-kappa B p50 Subunit
  • Rela protein, rat
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Peroxidase