PMID- 16271232 OWN - NLM STAT- MEDLINE DCOM- 20070123 LR - 20091119 IS - 0529-5815 (Print) IS - 0529-5815 (Linking) VI - 43 IP - 19 DP - 2005 Oct 1 TI - [Role of p38 mitogen-activated protein kinase in the pathogenesis of stress ulcer]. PG - 1284-7 AB - 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. CONCLUSION: p38 MAPK might have an important role in the pathogenesis of stress ulcer. FAU - Jia, Yi-tao AU - Jia YT AD - Department of Burns, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. FAU - Wei, Duo AU - Wei D FAU - Xia, Zhao-fan AU - Xia ZF FAU - Tian, Jian-guang AU - Tian JG LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Wai Ke Za Zhi JT - Zhonghua wai ke za zhi [Chinese journal of surgery] JID - 0153611 RN - 0 (Interleukin-1) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Disease Models, Animal MH - Interleukin-1/genetics MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Stomach Ulcer/enzymology/*etiology/genetics MH - Stress, Physiological/*complications MH - Tumor Necrosis Factor-alpha/genetics MH - p38 Mitogen-Activated Protein Kinases/metabolism/*physiology EDAT- 2005/11/08 09:00 MHDA- 2007/01/24 09:00 CRDT- 2005/11/08 09:00 PHST- 2005/11/08 09:00 [pubmed] PHST- 2007/01/24 09:00 [medline] PHST- 2005/11/08 09:00 [entrez] PST - ppublish SO - Zhonghua Wai Ke Za Zhi. 2005 Oct 1;43(19):1284-7.