title: Sialyl Lewis X analog attenuates gastric microcirculatory disturbance and gastric mucosal erosion induced by thermal injury in rats.
abstract: OBJECTIVE
  We hypothesize that selectins, which are adhesion molecules, are involved in the pathogenesis of stress-induced gastropathy. We therefore investigated whether the novel Sialyl Lewis X (SLex) analog, which is a clinically available antagonist of selectins, attenuate gastric mucosal lesions induced by thermal injury.
  
  
  METHODS
  Male Wistar rats were anesthetized and a 30% full-skin thickness dorsal burn was inflicted on each rat. The SLex analog was administrated into the jugular vein 30 min before and 2.5 h after the thermal injury. Saline was administered to the vehicle group. The distribution of E-selectin immunoreactivity on the luminal side of the gastric mucosal microvascular network was observed by immunohistochemical methods. Active oxygen species were measured by the chemiluminescence method. Rolling leukocytes and endothelial damage, investigated by using Monastral Blue B (MBB), of the gastric mucosal microvascular network were observed through an intravital microscope.
  
  
  RESULTS
  A high intensity of E-selectin fluorescence was observed on the luminal surface of the venular endothelial cells 5 h after thermal injury in the vehicle group. However, E-selectin-associated fluorescence was almost negligible in the non-injury group and in the SLex analog group. The SLex analog also attenuated the rolling of leukocytes in the venules, venular deposits of MBB, luminol-dependent chemiluminescence activities, and gastric mucosal lesion formation.
  
  
  CONCLUSIONS
  It is suggested that the selectin family is involved in gastric microcirculatory disturbance and the pathogenesis of gastric mucosal lesions after thermal injury. A novel preventive therapy using the SLex analog is considered to effectively protect both gastric microcirculation and the gastric mucosa in rats with thermal injury.
authors.affiliation: Department of Surgery, School of Medicine, Keio University and Center for Basic Research, The Kitasato Institute, Tokyo, Japan. hideki@ishikawa.email.ne.jp
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Yoshida
authors.forename: Go
authors.initials: G
authors.lastname: Wakabayashi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nakamura
authors.forename: Motohide
authors.initials: M
authors.lastname: Shimazu
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
mesh_terms: D000818:Animals; D002056:Burns / Q000473:pathology* / Q000503:physiopathology*; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D036904:Leukocyte Rolling; D008163:Luminescent Measurements; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009844:Oligosaccharides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D013270:Stomach / Q000098:blood supply*; D014699:Venules / Q000378:metabolism
chemical_list: D019040:E-Selectin; C102020:LX 0104; D009844:Oligosaccharides