The role of mitogen-activated protein kinases and the participation of intestinal congestion in total hepatic ischemia-reperfusion injury.
OBJECTIVE
The mitogen-activated protein kinase (MAPK) pathways are comprised of key regulatory proteins that control the cellular responses to both proliferation and stress signals. This study was performed to examine the degree of liver damage and MAPK activation induced by ischemia of varying durations, and the association between intestinal congestion and liver dysfunction after hepatic ischemia-reperfusion injury.


METHODS
Male Sprague-Dawley rats were divided into five groups: sham-operated controls (no hepatic ischemia); 15, 30, or 45 min of total hepatic ischemia; or 45 min of total hepatic ischemia with a portosystemic shunt. Serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, interleukin-1beta and tumor necrosis factor-alpha, as well as liver tissue blood flow were measured. Liver was also sampled for MAPK analysis and histopathological examination.


RESULTS
Total hepatic ischemia for over 30 min, with intestinal congestion, caused severe liver damage and an inflammatory cytokine response. A portosystemic shunt attenuated ischemia-reperfusion injury and inhibited inflammatory cytokine expression. Extracellular signal-regulated kinase was markedly phosphorylated in all groups other than the sham-operated group. p38 MAPK and c-Jun N-terminal kinase were highly phosphorylated in all groups receiving 30 min or more of ischemia.


CONCLUSIONS
Prolonged warm total hepatic ischemia-reperfusion injury is associated with small intestinal congestion; a portosystemic shunt reduces liver damage by inhibiting inflammatory cytokine expression. MAPKs are markedly phosphorylated after reperfusion.
Kobayashi
Mitsunobu
M
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Takeyoshi
Izumi
I
Yoshinari
Daisuke
D
Matsumoto
Koshi
K
Morishita
Yasuo
Y
D000818:Animals; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007422:Intestines / Q000098:blood supply*; D008107:Liver Diseases / Q000201:enzymology* / Q000209:etiology / Q000473:pathology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011170:Portasystemic Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology* / Q000209:etiology / Q000473:pathology*; D012720:Severity of Illness Index; D013997:Time Factors
D020928:Mitogen-Activated Protein Kinases