title: Alpha 2A-adrenoreceptor blockade improves sepsis-induced acute lung injury accompanied with depressed high mobility group box-1 levels in rats.
abstract: OBJECTIVE
  To investigate the effects of α2A-adrenoreceptor blockade on acute lung injury (ALI) and high mobility group box-1 protein (HMGB1) expression in a rat model of sepsis.
  
  
  METHODS
  Sepsis was induced in male rats by cecal ligation and puncture (CLP). Thirty adult male Sprague-Dawley rats were equally randomized to the Sham group, the CLP group, and the CLP+maleate group. Five hours after CLP, rats received an intraperitoneal injection of BRL-44408 maleate or the same volume of vehicle. Serum levels of TNF-α, IL-6, IL-10, HMGB1, and norepinephrine were measured at baseline, 6, 18, and 24h after CLP. Lung TNF-α, IL-6, IL-10, immunohistochemical and western blotting analysis of HMGB1, nuclear factor (NF)-κB activation, myeloperoxidase (MPO) activity, histological scores, and wet-to-dry weight ratio were determined 24h after CLP. In additional CLP and CLP+maleate groups, the 7 day survival rate was evaluated.
  
  
  RESULTS
  Compared with the CLP group, serum TNF-α at 6h, HMGB1 at 18 and 24h, and norepinephrine at 6 and 18 h after CLP decreased in the CLP+maleate group. Lung TNF-α, IL-6, and HMGB1 expressions decreased at 24h after CLP. NF-κB activation, MPO activity, histological scores, and wet-to-dry weight ratio were lower in the CLP+maleate group than the CLP group. There was no significant difference in 7 day survival rate between the CLP and CLP+maleate groups.
  
  
  CONCLUSIONS
  The α2A-adrenoreceptor blockade by a specific antagonist maleate improves sepsis-induced acute lung injury accompanied with depressed HMGB1 expression in rats. The mechanism seemed to be mediated partly through downregulation of the signal transductions of the NF-κB pathway.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Mu-huo
authors.initials: MH
authors.lastname: Ji
authors.forename: Xiao-ling
authors.initials: XL
authors.lastname: Zhu
authors.forename: Fang-fang
authors.initials: FF
authors.lastname: Liu
authors.forename: Guo-min
authors.initials: GM
authors.lastname: Li
authors.forename: Mi
authors.initials: M
authors.lastname: Tian
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Yun-xia
authors.initials: YX
authors.lastname: Fan
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jian-jun
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D002432:Cecum / Q000382:microbiology / Q000601:surgery; D015536:Down-Regulation; D004789:Enzyme Activation; D024243:HMGB1 Protein / Q000097:blood* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D054833:Isoindoles / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D018805:Sepsis / Q000150:complications / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D024243:HMGB1 Protein; D007093:Imidazoles; D015850:Interleukin-6; D054833:Isoindoles; D016328:NF-kappa B; D018341:Receptors, Adrenergic, alpha-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009195:Peroxidase; D009638:Norepinephrine; C072125:BRL 44408