Role of inhibition of p38 mitogen-activated protein kinase in liver dysfunction after hemorrhagic shock and resuscitation

Abstract Background The liver is one of the organs most frequently affected by trauma and hemorrhagic shock; the exact role of p38 mitogen-activated protein kinase (MAPK) activation in response to hepatic hemorrhagic shock/resuscitation (HS/R) remains unclear. Materials and methods C57Bl/6 mice were divided into four groups: sham-operated group, SB-only group, control group, and SB + HS/R group. Hepatocellular injury (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and tumor necrosis factor (TNF-α) and interleukin (IL-1β) messenger ribonucleic acid (mRNA) expression in the liver were assessed 6 h after resuscitation, p38 MAPK activation in the liver was assessed at 30 min after resuscitation. Results p38 MAPK activation was higher in the control group than other groups 30 min after resuscitation. p38 MAPK activation level in the SB + HS/R group did not change significantly compared with that of sham and SB-only groups, but was significantly lower than that in the control group. The TNF-α mRNA expression in the control group was significantly higher than that in the sham group. The TNF-α mRNA levels after HS/R in the SB + HS/R group were significantly lower than those in the control group and were roughly the same as those in the sham and SB-only groups. IL-1β mRNA expression showed similar changes in the four groups. Serum ALT and AST levels in the control group were significantly higher than those in the sham group. The increase in serum ALT and AST levels after HS/R in the SB + HS/R group was significantly less pronounced than that in the control group and markedly higher than that in the sham group. Conclusions p38 MAPK was phosphorylated during the HS/R process. Inhibiting the activation of p38 MAPK may attenuate HS/R injury to the liver.