Effect of hirudin on the levels of acute lung injury rat tumor necrosis             factor-α and matrix metalloproteinase-12.
The aim of this study was to observe the effect of hirudin on the expression of lung tissue protease activated receptor-1 (PAR-1) and the correlation between inflammation factors and the expression of PAR-1 after hirudin pre-treatment and to provide the theoretical basis for the treatment of lung injury by hirudin. Wistar rats of the model group were intraperitoneally administered endotoxin by injection (LPS 10 mg/kg) to copy acute lung injury (ALI) animal models, while the rats of the control group were injected with an equal amount of physiological saline. The rats of the hirudin groups were injected with hirudin and endotoxin intraperitoneally at the same time. The lung tissue was stained by HE dye to detect tumor necrosis factor α (TNF-α) and matrix metallo-proteinase 12 (MMP12) content. RT-PCR was applied to test PAR-1 mRNA expression. The results showed that the expression of PAR-1 mRNA of lung tissue increased significantly, but declined with the increased doses of hirudin when lung injury due to endotoxin occurred. The content of TNF-α and MMP12 was significantly lower compared to that of the endotoxin group. The difference was statistically significant (p<0.05). Hirudin reduced the release of TNF-α and MMP12 in mice by inhibiting the production of PAR-1 and reduced the content of TNF-α and MMP12. Thus, we deduced that hirudin inhibits the inflammation and fibrosis caused by lung injury and plays a role in lung protection as an anti-inflammatory mediator.
Department of Respiratory, The 2nd Affiliated Hospital, Harbin Medical University, Nangang, Harbin 150086, PR China.
Yongxia
Y
Bao
Ying
Y
Geng
Hui
H
Jing
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D005343:Fibrinolytic Agents; D006629:Hirudins; D008070:Lipopolysaccharides; D044463:Receptor, PAR-1; D014409:Tumor Necrosis Factor-alpha; D053508:Matrix Metalloproteinase 12