[Protective effect of remifentanil preconditioning against hepatic ischemia-reperfusion injury in rats: role of p38 mitogen-activated protein kinases].
OBJECTIVE
To assess the role of p38 mitogen-activated protein kinases (p38MAPK) in the protective effect of remifentanil preconditioning (RPC) on hepatic ischemia-reperfusion injury in rats.


METHODS
Ninety-six male SD rats were randomly assigned into sham-operated group, ischemia-reperfusion group (I/R group), RPC group, and SB (an inhibitor of p38 MAPK) +RPC group. The rats were sacrificed at the end of reperfusion, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured. HE staining was used to observe the hepatic histopathological changes, and Western blotting was employed to examine p38MAPK and pp38MAPK protein expression. TUNEL staining was used to examine cell apoptosis in the liver tissues.


RESULTS
Compared with sham-operated group, I/R group showed significantly increased serum levels of AST, ALT, TNF-α and IL-1β with obvious histopathological changes and cell apoptosis in the liver. RPC significantly decresed the elevated serum levels of AST, ALT, TNF-α and IL-1β and lessened hepatic histopathological changes, and caused reduced p38MAPK phosphorylation and hepatic cell apoptosis index. The protective effects of RPC were abolished by SB 203580 pretreatment.


CONCLUSIONS
RPC attenuates the production of inflammatory factors by activating p38MAPK signal pathway to improve hepatic ischemia-reperfusion injury, and these effects can be blocked by SB203580, a p38MAPK inhibitor.
Department of Anesthesiology, Xi'an Jiaotong University College of Medicine, Xi'an, China. zhaogemzk@sohu.com
Ge
G
Zhao
Zheng-chun
ZC
Chen
Xin
X
Shen
Ya-li
YL
Chen
Yi
Y
Lv
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D007093:Imidazoles / Q000494:pharmacology; D053583:Interleukin-1beta / Q000097:blood; D007511:Ischemia / Q000503:physiopathology; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply*; D020935:MAP Kinase Signaling System; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists; D000077208:Remifentanil; D015427:Reperfusion Injury / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D007093:Imidazoles; D053583:Interleukin-1beta; D010880:Piperidines; D011725:Pyridines; D011957:Receptors, Opioid; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D000077208:Remifentanil