[Effect of heparin upon inflammatory reaction of endotoxin-induced acute lung injury in rat].
OBJECTIVE
To investigate the effects of heparin upon inflammatory reaction and associated mechanism of endotoxin-induced acute lung injury (ALI) in rat.


METHODS
Thirty-six male Sprague-Dawley rats were randomly divided into three equal groups namely: ALI group, heparin treatment group and normal control group. The ALI rats were induced by injecting endotoxin intravenously and sacrificed at 4 h after model establishment. The lung histology was scored by a modification of Smith technique. The albumin permeability of pulmonary microvascular (P(alb)) was measured by single nuclide tracer technique. Tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and von Willebrand factor (vWF) levels of serum were determined using commercial enzyme-linked immunosorbent assay kits. The expressions of lung tissue extacellular signal-regulated kinases (ERK)-1/2, P38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinases (JNK) were determined by Western blotting.


RESULTS
The Smith lung injury score in heparin treatment group and ALI group were (5.00 +/- 1.26) and (8.00 +/- 1.09) respectively. The values were significantly higher than that of normal control group (0.67 +/- 0.52, both P < 0.01). However, the Smith lung injury score in heparin treatment group was significantly lower than that of ALI group (P < 0.01). The P(alb), TNF-alpha, IL-6 and vWF of heparin treatment group were (0.28 +/- 0.04), (1.92 +/- 0.35) microg/L, (1.22 +/- 0.13) ng/ml and (24.9 +/- 4.0) U/L respectively. The values were significantly higher than those of normal control group [0.20 +/- 0.02, (0.51 +/- 0.09) microg/L, (0.23 +/- 0.05) ng/ml and (14.0 +/- 3.0) U/L respectively, all P < 0.01] but significantly lower than those of ALI group [(0.38 +/- 0.04), (2.77 +/- 0.37) microg/L, (1.62 +/- 0.13) ng/ml and (31.8 +/- 7.5) U/L respectively, all P < 0.01]. The lung tissue levels of phospho-ERK1/2 and phospho-P38 MAPK expressions of heparin treatment group were markedly higher than those of normal control group, whereas markedly lower than those of ALI group. There was no marked difference of phospho-JNK expression in all three groups.


CONCLUSIONS
Heparin markedly inhibits the expressions of phospho-ERK1/2 and phospho-P38 MAPK, down-regulates the inflammatory reaction, attenuates the endothelial permeability of pulmonary vasculature and significantly improves endotoxin-induced lung injury in rats.
Sun
Hui-Ming
HM
Department of Respiratory Diseases, Clinical School of Nanjing University, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, China.
Shi
Yi
Y
Song
Yong
Y
Lin
Xin-Qing
XQ
Shen
Xiao-Kun
XK
Hong
Ling-Zhi
LZ
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004730:Endothelium, Vascular / Q000473:pathology; D004731:Endotoxins / Q000009:adverse effects; D006493:Heparin / Q000494:pharmacology*; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; D006493:Heparin; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases