Therapeutic effects and anti-inflammatory mechanisms of heparin on acute lung injury in rabbits.
OBJECTIVE
The objectives were to investigate the potential beneficial effects and molecular mechanisms of heparin and low-molecular-weight heparin (LMWH) on acute lung injury (ALI).


METHODS
Forty-eight rabbits were randomized into four groups: normal control group (Group A), lipopolysaccharide (LPS) group (Group B), LPS + heparin group (Group C), and LPS + LMWH group (Group D). The rabbit ALI model was established by intravenous (IV) injection with LPS. Alveolar-arterial O2 difference (P(A-a)O2), serum tumor necrosis factor alpha (TNF-alpha), circulating p38 mitogen-activated protein kinase (p38 MAPK) levels, lung nuclear factor (NF)-kappaB levels, and lung dry/wet (D/W) ratio were measured, and the lung injury scores were calculated.


RESULTS
Lipopolysaccharide caused significant increases in P(A-a)O2, serum TNF-alpha, expression of p38 MAPK in polymorphonuclear neutrophils (PMNs), the lung injury scores, and nuclear factor-kappaB (NF-kappaB) activity in the lung tissue and caused a decrease in lung D/W ratio. A positive linear correlation was found between p38 MAPK and TNF-alpha at 1, 2, 4, and 6 hours (r = 0.68, 0.92, 0.93, and 0.93, respectively) and between NF-kappaB and p38 MAPK and TNF-alpha at 6 hours (r = 0.94 and 0.83, respectively). IV heparin or LMWH given after LPS treatment attenuated these changes in inflammatory response, oxygenation, p38 MAPK expression, and NF-kappaB activation.


CONCLUSIONS
The anti-inflammatory mechanisms of heparin in ALI may be inhibiting p38 MAPK and NF-kappaB activities, and then TNF-alpha overexpression, thus alleviating the inflammatory reaction.
Wang
Meitang
M
Emergency Department, Shanghai Changhai Hospital, Shanghai, China.
He
Jian
J
Mei
Bin
B
Ma
Xiuqiang
X
Huo
Zhenglu
Z
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D016328:NF-kappa B / Q000097:blood; D010100:Oxygen / Q000378:metabolism; D011817:Rabbits; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000097:blood
D006495:Heparin, Low-Molecular-Weight; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin; D048051:p38 Mitogen-Activated Protein Kinases; D010100:Oxygen