title: Unfractionated heparin attenuates lung vascular leak in a mouse model of sepsis: role of RhoA/Rho kinase pathway.
abstract: BACKGROUND
  Excessive vascular permeability is a characteristic feature of ALI. We have previously demonstrated that UFH prevents LPS-induced disruption of endothelial barrier function in vitro. It was the objective of this study to determine whether UFH may attenuate endotoxin-induced lung vascular leak in mice and to further explore the possible underlying mechanisms.
  
  
  METHODS
  C57BL/6J mice were randomly divided into the control, LPS and LPS plus UFH groups. Sepsis was induced by intraperitoneal injection of LPS at a dose of 30 mg/kg. Mice in the LPS plus UFH group were intravenously received 8 units UFH (heparin sodium) diluted in 20 μl sterile saline at 0.5 h before the injection of LPS.
  
  
  RESULTS
  1) UFH pretreatment attenuated LPS-induced histopathological changes in Lung at 6 h; 2) Pretreatment of mice with UFH ameliorated LPS-induced lung edema and lung vascular leak at 6 h; 3) UFH pretreatment dramatically inhibited RhoA and ROCK activation in the lung tissues of LPS-treated mice (3 and 6 h). 4) UFH pretreatment significantly down-regulated ROCK1 gene expression, but did not affect the increased expression of ROCK2 mRNA in the lung tissues of LPS-treated mice at 3 or 6 h.
  
  
  CONCLUSIONS
  These data suggest that UFH may attenuate endotoxin-induced lung vascular leak by regulating RhoA/Rho kinase pathway.
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
authors.forename: Renyu
authors.initials: R
authors.lastname: Ding
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhao
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D019559:Capillary Leak Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008168:Lung / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; D008070:Lipopolysaccharides; D006493:Heparin; D054460:rho-Associated Kinases
keywords: ALI; Acute lung injury; LPS; Lipopolysaccharide; MLC; MYPT1; Myosin light-chain; Myosin phosphatase target subunit 1; ROCK; RT-PCR; Reverse Transcribed-Polymerase Chain Reaction; Rho-kinase; RhoA; UFH; Unfractionated heparin; acute lung injury; sepsis; unfractionated heparin; vascular barrier function