Heparin attenuates lipopolysaccharide-induced acute lung injury by inhibiting nitric oxide synthase and TGF-β/Smad signaling pathway.
BACKGROUND
Heparin, a potent blood anticoagulant, has been shown to exert a variety of pharmacological activities. The purpose of this study was to investigate whether heparin has a beneficial effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and to further explore the possible underlying mechanisms.


METHODS
Adult Sprague-Dawley rats were randomly assigned into the control, heparin, LPS, and LPS plus heparin groups. ALI was induced by intratracheal instillation of LPS at a dose of 1 mg/kg. Rats in the LPS plus heparin group were intravenously received 50 U/ kg heparin every 1 h after the induction of ALI.


RESULTS
We found that heparin significantly improved LPS-induced lung pathological changes, inhibited myeloperoxidase (MPO) activity, and reduced malondialdehyde (MDA) level and lung wet/dry weight ratio. Heparin also inhibited the release of tumor necrosis factor (TNF)-α and interleukin (IL)-6, and markedly decreased the expression of inducible nitric oxide synthase (iNOS) in lung tissues and thus prevented nitric oxide (NO) release in response to LPS challenge. Additionally, heparin decreased the expression of transforming growth factor-β1 (TGF-β1), p-Smad 2, and p-Smad 3, which are all important molecules of the TGF-β1/Smad signaling pathway.


CONCLUSIONS
Heparin significantly ameliorated the lung injury induced by LPS in rats via the inhibition of nitric oxide synthase expression and the TGF-β/Smad pathway. Heparin may be a potential therapeutic reagent for treating ALI in the future.
Department of Intensive Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
En
E
Mu
Renyu
R
Ding
Xin
X
An
Xin
X
Li
Song
S
Chen
Xiaochun
X
Ma
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D016896:Treatment Outcome
D000925:Anticoagulants; D008070:Lipopolysaccharides; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D006493:Heparin; D019001:Nitric Oxide Synthase