Effect of ulinastatin combined with ischemic preconditioning on hepatic ischemia-reperfusion injury in rats

Objective To investigate the effect of ulinastatin (UTI) preconditioning combined with ischemic preconditioning (IPC) on hepatic ischemia-reperfusion (IR) injury in rats and possible mechanism of action.Methods A total of 50 male Sprague-Dawley rats were randomly divided into sham-operation group, IR group, IPC group, UTI group, and UTI-IPC group (UCI group) .Blood samples were collected from the inferior vena cava after surgery and liver tissue samples were also collected.The serum levels of aspartate aminotransferase (AST) , alanine aminotransferase (ALT) , and tumor necrosis factor-α (TNF-α) , the levels of myeloperoxidase (MPO) and nuclear factor-kappa B (NF-κB) in the liver tissue, and wet/dry weight ratio were determined, and pathomorphological changes of the liver tissue were observed under a light microscope.A one-way analysis of variance was used for comparison of continuous data between groups, and the LSD-t-test was used for further comparison between two groups.Results The IR, IPC, UTI, and UCI groups had significantly higher serum levels of ALT, AST, and TNF-α, levels of MPO and NF-κB in the liver tissue, and wet/dry weight ratio than the sham-operation group (all P < 0.05) ; the IPC, UTI, and UCI groups had significantly lower levels than the IR group (all P < 0.05) , the UTI group had significantly lower levels than the IPC group (all P < 0.05) , and the UCI group had significantly lower levels than the IPC and UTI groups (all P < 0.05) .Liver pathological examination showed that compared with the sham-operation group, the IR, IPC, UTI, and UCI groups had significantly greater liver injury (all P < 0.05) , while the IPC, UTI, and UCI groups had a significantly lower degree of liver injury than the IR group (all P < 0.05) , the UTI group had significantly slighter liver injury than the IPC group (P < 0.05) , and the UCI group had significantly slighter liver injury than the IPC and UTI groups (both P < 0.05) .Conclusion Both UTI and UCI have a protective effect against hepatic IR injury, and the combination of UTI and UCI significantly enhances such protective effect, possibly by inhibiting the expression of NF-κB, reducing the release of TNF-α and MPO, and alleviating liver inflammatory response.