[Role of p38 mitogen-activated protein kinase in the pathogenesis of stress ulcer].
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.
Jia
Yi-tao
YT
Department of Burns, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Wei
Duo
D
Xia
Zhao-fan
ZF
Tian
Jian-guang
JG
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*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases