Inhibition of p38 mitogen-activated protein kinase may decrease intestinal epithelial cell apoptosis and improve intestinal epithelial barrier function after ischemia- reperfusion injury

• Published in: World journal of gastroenterology : WJG Vol. 11; no. 5; pp. 656 - 660
• Main Authors: Zheng, Shu-Yun, Fu, Xiao-Bing, Xu, Jian-Guo, Zhao, Jing-Yu, Sun, Tong-Zhu, Chen, Wei
• Format: Journal Article
• Language: English
• Published: United States Wound Healing and Cell Biology Laboratory, Burns Institute, 304 Medical Department, The General Hospital of PLA, Trauma Center of Postgraduate Medical College, Beijing 100037, China 07.02.2005; Central Hospital of Jinghua City, Jinghua 321000,Zhejiang Province, China%Wound Healing and Cell Biology Laboratory, Burns Institute, 304 Medical Department, The General Hospital of PLA, Trauma Center of Postgraduate Medical College, Beijing 100037, China%Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, China; Baishideng Publishing Group Inc
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Basic Research; Biological Transport - drug effects; Biological Transport - physiology; Enzyme Inhibitors - pharmacology; Imidazoles - pharmacology; Intestinal Mucosa - enzymology; Intestinal Mucosa - pathology; Lactic Acid - blood; Male; p38; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Pyridines - pharmacology; Rats; Rats, Wistar; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; 多次灌注伤; 局部缺血; 抑制作用作用; 有丝分裂; 活性蛋白; 消化道; 细胞调亡; 肠上皮细胞; 蛋白激酶; 阻塞功能; Intestines; Ischemia-reperfusion injury; p38mitogen-activated protein kinase; Apoptosis
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v11.i5.656

AIM: To investigate the role of p38 mitogen-activated protein kinase in rat small intestine after ischemia-reperfusion (I/R) insult and the relationship between activation of p38 MAPK and apoptotic cell death of intestine.METHODS: Ninety Wistar rats were divided randomly into three groups, namely sham-operated group (C), I/R vehicle group (R) and SB203580 pre-treated group (S). In groups R and S, the superior mesenteric artery (SMA) was separated and occluded for 45 min, then released for reperfusion for0.25, 0.5, 1, 2, 6, 12 and 24h. In group C, SMA was separated without occlusion. Plasma D-lactate levels were examined and histological changes were observed under a light microscope. The activity of p38 MAPK was determined by Western immunoblotting and apoptotic cells were detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUDP-biotin nick end labeling (TUNEL).RESULTS: Intestinal ischemia followed by reperfusion activated p38 MAPK, and the maximal level of activation (7.3-fold vs sham-operated group) was reached 30 rain after I/R. Treatment with SB 203580, a p38 MAPK inhibitor, reduced intestinal apoptosis (26.72+3.39% vs 62.50+3.08% in I/R vehicle,P<0.01) and decreased plasma D-lactate level (0.78±0.15mmol/L in I/R vehicle vs 0.42±0.17mmol/L in SB-treated group) and improved post-ischemic intestinal histological damage.CONCLUSION: p38 MAPK plays a crucial role in the signal transduction pathway mediating post-ischemic intestinal apoptosis, and inhibition of p38 MAPK may attenuate ischemia-reperfusion injury.