[The modulating role of p38 mitogen-activated protein kinase in the expression of tumor necrosis factor-alpha in hepatic cells and its role in hepatic injury in severely burned rats].

ABSTRACT

OBJECTIVE: To investigate The modulating role of p38 mitogen-activated protein kinase (MAPK) in the expression of tumor necrosis factor-alpha in hepatic cells and its role in hepatic injury in severely burned rats. METHODS: Twenty-four adult healthy male SD rats were randomly divided into three groups (8 rats in each group) sham group, burn group, and burn with SB203580 group. A rat model of full-thickness burn injury covering 30% total body surface area (TBSA) was reproduced. The specific inhibitor of p38MAPK (SB203580 in 10 mg/kg) was given to the rats in the burn with SB203580 group at 15 minutes and 12 hours after burn. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured at 24 postburn hours (PBHs). The TNF-alpha mRNA expression in the liver was determined by real-time reverse transcription polymerase chain reaction, and the expression levels of p38MAPK and phosphor-p38MAPK in the liver were determined by Western blot analysis. RESULTS: The serum levels of AST and ALT, and the expression of TNF-alpha mRNA in liver cells were significantly higher in burn group than those in sham and SB203580 groups (P < 0.05 or 0.01), but there was no difference between the two latter groups. It was indicated by Western blot results that there was no difference of p38MAPK expression in rat liver among the three groups (P > 0.05). The phospho-p38MAPK expression ratio among sham, burn and burn with SB203580 groups was 1.003.901.10. The phospho-p38MAPK expression was significantly lower in burn with SB203580 group than that in burn group (P < 0.01), but there was no significant difference compared with that in sham group (P > 0.05). CONCLUSION: The postburn activated p38MAPK in rat liver after severe burn injury enhances the expression of TNF-alpha mRNA and participates in the development of postburn hepatic injury.