IRF-1' role in liver ischemia reperfusion injury in mice

Abstract

Objective To investigate the role of interferon regulatory factor-1 (IRF-1) in liver ischemia/reperfusion (IR) injury and its underlying mechanism, and identify effective managements in alleviating liver IR injury. Methods Three groups of mice models with liver IR injury were well established, including control group (S), warm liver IR injury group (IR) and recombinant IRF-1 group (IRF-1). The levels of mRNA and protein, liver function and pathological changes of liver tissue were detected in group S and group IR. Additionally, the marker of IRF-1, p-Stat1, p-P38, PARP1 and Caspase-3 were measured and PCNA expression was determined in group IR and group IRF-1 mice with 6-hour liver IR injury. Results IRF-1mRNA and protein and the levels expression of proteins were significantly elevated with peak occurred after 6-hour IR injury, which was statistic difference compare to the group S (t2h=-3.512, t6h=-4.247, t12h=-4.088, t24h =-3.851; P<0.05). Serum ALT and AST of mice detected in group IR were higher than group S at all endpoints (tALT=4.931, 4.592, 4.277, 4.809; tAST=4.980, 4.617, 4.336, 4.915; P<0.05). Furthermore, pathological damage change was more distinct compared with group S. The elevated levels of IRF-1, p-Stat1, p-P38, PARP1 and Caspase-3 and decreased PCNA expression were determined in mice models with recombinant IRF-1 intervention. Conclusion IRF-1 expression could be closely correlated with liver IR injury, and its underlying mechanism may be attributed to activation of JNK MAPK protein and inhibition of PCNA expression. Key words: Liver ischemia; Ischemia-reperfusion; Reperfusion injury; Interferon regulatory factor-1(IRF-1)