Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model
Abstract
:1. Introduction
2. Results
2.1. The Effects of Endotoxin Stimulation on VILI Are Partially Inversed by Enoxaparin
2.2. The Effects of Endotoxin-Stimulated MV-Induced Neutrophil Sequestration, Oxygen Radicals and HIF-1α mRNA Activation Are Partially Inhibited by Enoxaparin
2.3. The Effects of Endotoxin-Stimulated MV-Induced HIF-1α Expression Are Partially Reduced by Enoxaparin
2.4. The Effects of Endotoxin-Stimulated MV-Induced Lung Injuries, Hypoxemia and Impaired Respiratory Function Are Partially Inhibited in HIF-1α Deficient Mice
2.5. The Effects of Endotoxin-Stimulated MV-Induced Expression of Caspase-3 and Epithelial Apoptosis Are Partially Suppressed in HIF-1α Deficient Mice and Enoxaparin
3. Discussion
4. Materials and Methods
4.1. Ethics of Experimental Animals
4.2. Experimental Groups
4.3. Ventilator Protocol
4.4. Lipopolysaccharide Administration
4.5. Enoxaparin Administration
4.6. Whole Body Plethysmography
4.7. Measurement of Inflammatory Cytokines
4.8. Real Time Polymerase Chain Reaction
4.9. Immunoblot Analysis
4.10. Immunohistochemistry
4.11. Histopathologic Grading of VILI
4.12. Analysis of Data
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ALI | acute lung injury |
BAL | bronchoalveolar lavage |
FiO2 | fraction of inspired oxygen |
HIF | hypoxia-inducible factor |
IL | interleukin |
LMWH | low-molecular-weight heparin |
LPS | lipopolysaccharide |
MIP-2 | macrophage inflammatory protein-2 |
MPO | myeloperoxidase |
MV | mechanical ventilation |
ROS | reactive oxygen species |
SOD | sodium dismutase |
TEM | transmission electron microscopy |
TNF-α | tumor necrosis factor-α |
TUNEL | terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay |
VEGF | vascular endothelial growth factor |
VILI | ventilator-induced lung injury |
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Li, L.-F.; Liu, Y.-Y.; Lin, S.-W.; Chang, C.-H.; Chen, N.-H.; Hung, C.-Y.; Lee, C.-S. Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model. Int. J. Mol. Sci. 2020, 21, 3097. https://doi.org/10.3390/ijms21093097
Li L-F, Liu Y-Y, Lin S-W, Chang C-H, Chen N-H, Hung C-Y, Lee C-S. Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model. International Journal of Molecular Sciences. 2020; 21(9):3097. https://doi.org/10.3390/ijms21093097
Chicago/Turabian StyleLi, Li-Fu, Yung-Yang Liu, Shih-Wei Lin, Chih-Hao Chang, Ning-Hung Chen, Chen-Yiu Hung, and Chung-Shu Lee. 2020. "Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model" International Journal of Molecular Sciences 21, no. 9: 3097. https://doi.org/10.3390/ijms21093097