title: The role of mitogen-activated protein kinases and the participation of intestinal congestion in total hepatic ischemia-reperfusion injury.
abstract: 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.
authors.affiliation: Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Izumi
authors.initials: I
authors.lastname: Takeyoshi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshinari
authors.forename: Koshi
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishita
mesh_terms: 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
chemical_list: D020928:Mitogen-Activated Protein Kinases