[The role of p38 MAPK pathway in ischemia-reperfusion injury of isolated liver].
OBJECTIVE
To study the effect of p38 MAPK activity on isolated rabbit liver during the period of cold preservation and reperfusion.


METHODS
Based on the cold preservation-reperfusion model of isolated rabbit livers, according to the concentration of SB202190 in the preservation solution which was a specific p38 MAPK inhibitor, the isolated livers were divided into 4 groups, six in each A, B, C and D. Liver tissue samples and blood samples were harvested at different time points: before and end of cold preservation, reperfusion for 5, 10, 15, 30, 60, and 120 minutes. The activity levels of p38 MAPK were detected by both western blot and immunoprecipitation. The function markers of isolated livers were detected with automatic biochemistry analyzer, and the levels of total bile after reperfusion were measured.


RESULTS
In normal rabbit liver tissues, p38 MAPK had low activity. During the cold preservation period, the activity of p38 MAPK elevated slightly. But during the reperfusion period, the activity of p38 MAPK changed markedly which elevated rapidly at the early stage and reached its peak value at 10 minutes, then decreased gradually to the normal level (7.6 +/-0.9) at 120 minutes. SB202190 could inhibit the activity in a dose-dependent manner. The peak values of p38 MAPK activity in group B,C and D were 42.5 +/-2.4, 10.1+/-1.4, and 7.6 +/-0.6 respectively, while 78.6 +/-6.1 in group A. During the reperfusion period, the levels of serum ALT, AST and ALP were higher in group A than those in any other group, alike the p38 MAPK activity, especially at 15 and 30 minutes. On the other hand, the total bile secretion volume was (10.2 +/-2.9) ml/100 g, (13.9 +/-1.3) ml/100 g, (15.6 +/-1.2) ml/100 g, and (16.0 +/-1.3) ml/100 g in group A, B, C and D respectively.


CONCLUSIONS
During the cold preservation- reperfusion period, p38 MAPK specific inhibitor SB202190 can lower the p38 MAPK activity, and ameliorate the isolated liver injury. Activation of p38 pathway is one of the important mechanisms to cause ischemia-reperfusion injury of isolated liver.
Wang
Yu
Y
General Surgery center of People's Liberation Army, General Hospital of Chengdu Military Region, Chengdu 610083, China.
Tian
Fu-zhou
FZ
Tang
Li-jun
LJ
Shi
Li
L
Zhang
Xiao-qiong
XQ
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000098:blood supply* / Q000166:cytology; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D015427:Reperfusion Injury / Q000201:enzymology* / Q000503:physiopathology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole