title: Effects of hydroxyethyl starch 130/0.4 on pulmonary capillary leakage and cytokines production and NF-kappaB activation in CLP-induced sepsis in rats.
abstract: BACKGROUND
  Sepsis and resulting multiple system organ failure are the leading causes of mortality in intensive care units. Hydroxyethyl starch (HES) 130/0.4 was a novel preparation, developed to improve the pharmacokinetics of current medium molecular weight HES solutions. This study was designed to explore the effects of HES 130/0.4 on pulmonary capillary permeability (PCP), production of cytokines, and activation of transcription factor in septic rats induced by cecal ligation and puncture (CLP).
  
  
  METHODS
  Adult male Sprague Dawley rats were randomly divided into six groups (six rats/group): saline controls (30 ml/kg); CLP plus saline (30 ml/kg); CLP plus HES (7.5, 15, or 30 ml/kg, respectively), and HES alone (30 ml/kg). Mean arterial blood pressure and heart rate were monitored during the experiment process. Myeloperoxidase (MPO) activity, wet/dry weight ratio, PCP, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, IL-10, and nuclear factor-kappa B (NF-kappaB) were investigated at 6 h.
  
  
  RESULTS
  We demonstrated that CLP could provoke significant injury in lung, characterized by increase in PCP, wet/dry weight ratio, MPO activity, TNF-alpha, IL-6, and IL-10 level, and NF-kappaB activation. Without obvious influence on systemic macro-hemodynamics, HES 15 ml/kg and 30 ml/kg significantly reduced CLP-induced elevation of pulmonary capillary permeability, wet/dry weight ratio, and production of IL-6. Meanwhile, HES 15 ml/kg increased IL-10 level and HES 7.5, 15, and 30 ml/kg suppressed MPO activity, TNF-alpha level, and NF-kappaB activation.
  
  
  CONCLUSIONS
  HES 130/0.4 can inhibit CLP-induced PCP by attenuating pulmonary inflammation and NF-kappaB activation in vivo.
authors.affiliation: Department of Anesthesiology Jinling Hospital, School of Medicine, Nanjing University, Nanjing, P. R. China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.forename: Manlin
authors.initials: M
authors.lastname: Duan
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002432:Cecum / Q000293:injuries; D016207:Cytokines / Q000378:metabolism*; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008026:Ligation; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D018805:Sepsis / Q000150:complications* / Q000276:immunology; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014951:Wounds, Stab
chemical_list: D016207:Cytokines; C485123:HES 130-0.4; D006895:Hydroxyethyl Starch Derivatives; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009195:Peroxidase