Inhibition of p38 mitogen-activated protein kinase may decrease intestinal epithelial cell apoptosis and improve intestinal epithelial barrier function after ischemia- reperfusion injury.
OBJECTIVE
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 for 0.25, 0.5, 1, 2, 6, 12 and 24 h. 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 min 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+/-0.15 mmol/L in I/R vehicle vs 0.42+/-0.17 mmol/L in SB-treated group) and improved post-ischemic intestinal histological damage.


CONCLUSIONS
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.
Zheng
Shu-Yun
SY
Wound Healing and Cell Biology Laboratory, Burns Institute, 304 Medical Department, The General Hospital of PLA, Trauma Center of Postgraduate Medical College, 51 Fu Cheng Road, Beijing 100037, China.
Fu
Xiao-Bing
XB
Xu
Jian-Guo
JG
Zhao
Jing-Yu
JY
Sun
Tong-Zhu
TZ
Chen
Wei
W
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology; D019344:Lactic Acid / Q000097:blood; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D019344:Lactic Acid; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580