title: [Role of p38 mitogen-activated protein kinase in the pathogenesis of stress ulcer].
abstract: OBJECTIVE
  To determine whether the activation of p38 mitogen-activated protein kinase (MAPK) is involved in the pathogenesis of stress ulcer.
  
  
  METHODS
  Model of stress ulcer was established with the treatment of rats with water-immersion restraint (WIR) stress. Ulcer index (UI) was macroscopically evaluated as a parameter of gastric mucosal lesions. Expression of phospho- and pan-p38 in gastric mucosa was detected using Western blot analysis. Tumor necrosis factor-alpha (TNF-alpha) and Interleukin 1beta (IL-1beta) gene expressions were analyzed by Northern blot analysis. As indicated in some experiments, rats were pretreated with intravenous injection of the specific p38 MAPK inhibitor CNI-1493 prior to WIR stress and then the changes of UI and TNF-alpha and IL-1beta mRNA expression were examined.
  
  
  RESULTS
  The p38 MAPK was persistently activated in the gastric mucosa of rats with WIR stress, with maximal activation after 1 h of stress [(6.8 +/- 3.2) fold of baseline levels, P < 0.01]. Inhibition of p38 MAPK activation with CNI-1493 led to a marked decrease in UI in WIR stress rats. Similarly, the increased gene expression of proinflammatory cytokines TNF-alpha and IL-1beta in gastric mucosa induced by WIR stress were significantly diminished by p38 MAPK inhibition.
  
  
  CONCLUSIONS
  p38 MAPK might have an important role in the pathogenesis of stress ulcer.
authors.affiliation: Department of Burns, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yi-tao
authors.initials: YT
authors.lastname: Jia
authors.forename: Duo
authors.initials: D
authors.lastname: Wei
authors.forename: Zhao-fan
authors.initials: ZF
authors.lastname: Xia
authors.forename: Jian-guang
authors.initials: JG
authors.lastname: Tian
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000235:genetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D013312:Stress, Physiological / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases