title: Sivelestat sodium hydrate attenuates acute lung injury by decreasing systemic inflammation in a rat model of severe burns.
abstract: OBJECTIVE
  Patients with severe burns often develop acute lung injury (ALI), systemic inflammatory response syndrome (SIRS) often complicates with ALI. Sivelestat sodium hydrate is an effective drug against ALI. However, the mechanisms of this beneficial effect are still poorly understood. In the current study, we evaluate the effects of sivelestat sodium hydrate on systemic and local inflammatory parameters (neutrophil elastase [NE], interleukin [IL]-8, matrix metalloproteinase [MMP] 2 and 9) in a rat model of severe burns and ALI. And to analyze the correlations between expression of NE and IL-8 and acute lung injury.
  
  
  METHODS
  48 Sprague-Dawley (SD) rats were divided into 3 groups: normal control group, severe burns injury group and severe burns treated with sivelestat sodium hydrate group (SSI). The lung water content and PaO2 were detected in each group. Pathological manifestations in each group were observed for pathology scoring in SD rats with acute lung injury. ELISA was used for detecting expression of NE and IL-8 in serum and BAL specimens of SD rats in each group. RT-PCR was used to detect mRNA expression of NE and IL-8 in lung tissues of each group. Western blotting was used for detecting protein expression of MMP-2 and MMP-9 in lung tissues of each group. SPSS 18.0 was used for statistical analysis.
  
  
  RESULTS
  The PaO2 was significantly increased after sivelestat sodium hydrate intravenous injection. Pathological score and water content of lung tissue were significantly decreased in SSI group compared with severe burns injury group, slightly higher than that normal control group. NE and IL-8 levels significantly decreased in serum, BAL and lung tissue specimens after sivelestat sodium hydrate intravenous injection; Expression of MMP-2 and MMP-9 were significantly up-regulated in severe burns group and showed no significantly changed after sivelestat sodium hydrate intravenous injection.
  
  
  CONCLUSIONS
  In a rat model of severe burns and ALI, administration of sivelestat sodium hydrate improved symptoms of ALI and significantly decreased inflammatory parameters NE and IL-8.
authors.affiliation: The Burn and Plastic Department, The First Affiliated Hospital of the University of Henan Science and Technology, Henan, China. 25852832@qq.com.
authors.forename: X-G
authors.initials: XG
authors.lastname: Xiao
authors.forename: H-G
authors.initials: HG
authors.lastname: Zu
authors.forename: Q-G
authors.initials: QG
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Huang
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001784:Blood Gas Analysis; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C508606:CXCL8 protein, human; D018836:Inflammation Mediators; D016209:Interleukin-8; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine