Effects of ischemic postconditioning on reperfusion injury in rat liver grafts after orthotopic liver transplantation

Abstract

The effects of ischemic postconditioning (IPostC) on ischemia reperfusion (IR) injury of liver grafts was examined in rats after orthotopic liver transplantation (OLT). Male Wistar rats were used as donors and recipients to establish a liver transplantation model. The animals were randomly divided into four groups: sham-operated (SO, n = 6), IR (n = 6), IPostC1 (n = 6) and IPostC2 (n = 6). IPostC was achieved by several intermittent interruptions of blood flow in the early phase of reperfusion. Several parameters of hepatic damage, oxidative stress, neutrophil infiltration and the expression of TNF-alpha and MIP-2 were detected as well as microscopic examination. Nitric oxide release and liver NO synthases (endothelial NO synthase and inducible NO synthase) expression were also measured. We observed that a significant reduction in alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase values in two IPostC groups when compared with IR group. The increases in hepatic malondialdehyde, and decreases in superoxide dismutase and reduced glutathione levels after orthotopic liver transplantation were significantly inhibited by IPostC. IR induced increase in hepatic myeloperoxidase content, TNF-alpha and MIP-2 expression were also lowered by IPostC. The increases in NO content and NOS protein expression were much more prominent in IPostC treated groups. Animals treated with IPostC presented minimal hemorrhage and reduced signs of liver injury. There was no significant difference between two IPostC treated groups. IPostC provided significant protection against IR injury to liver grafts. The protective effect of IPostC is closely related to the NO production following the increase in endothelial and inducible NO synthases expression and the suppression of tumor necrosis factor-alpha and macrophage inflammatory protein-2 overproduction.