Heparin rescues sepsis-associated acute lung injury and lethality through the suppression of inflammatory responses.
Heparin, a potent blood anticoagulant, is known to possess anti-inflammatory activity. In this work, we investigated whether heparin can ameliorate acute lung injury and lethal response in lipopolysaccharide (LPS)-induced mouse model of sepsis. We found that heparin effectively rescued lethality, improved lung pathological changes, inhibited myeloperoxidase (MPO) activity, and reduced malondialdehyde (MDA) level, lung wet/dry weight ratio and Evans blue values in LPS-induced septic mice. In addition, heparin also inhibited the release of tumor necrosis factor (TNF)-α, interleukin-6 (IL-6) and IL-1β in serum and decreased the expression of p-p38, nuclear factor κB (NF-κB) and p-c-SRC kinase in lungs of septic mice. Our findings suggest that heparin is capable of suppressing the lethal response and acute lung injury associated with sepsis, and support the notion that heparin may be a potential therapeutic agent for the conditions associated with septic shock.
Department of Intensive Care Medicine, First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, China.
Dongmei
D
Zhao
Renyu
R
Ding
Yiran
Y
Mao
Liang
L
Wang
Zhidan
Z
Zhang
Xiaochun
X
Ma
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000401:mortality; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000037:antagonists & inhibitors; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D006493:Heparin; D009195:Peroxidase; D019061:src-Family Kinases; D048051:p38 Mitogen-Activated Protein Kinases