Background: Hepatic ischemia-reperfusion (I/R) injury occurs in many clinical procedures. The molecular mechanisms responsible for hepatic I/R injury however remain unknown. Sphingolipids, in particular ceramide, play a role in stress and death receptor-induced hepatocellular death, contributing to the progression of several liver diseases including liver I/R injury. In order to further define the role of sphingolipids in hepatic I/R, systemic analysis of sphingolipids after reperfusion is necessary.
Methods: We investigated the lipidomic changes of sphingolipids in a rat model of warm hepatic I/R injury, by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry (DE MALDI-TOF-MS).
Results: The total amounts of ceramide and sphingomyelin and the intensity of most kinds of sphingolipids, mainly sphingomyelin, significantly increased at 1 hour after reperfusion (P < 0.05) and reached peaks at 6 hours after reperfusion (P < 0.01) compared to controls. Six new forms of ceramide and sphingomyelins appeared 6 hours after reperfusion, they were (m/z) 537.8, 555.7, 567.7, 583.8, 683.5 and 731.4 respectively. A ceramide-monohexoside (m/z) 804.4 (CMH(d18:1C22:1+Na)(+)) also increased after reperfusion and correlated with extent of liver injury after reperfursion.
Conclusions: Three main forms of sphingolipids, ceramide, sphingomyelin and ceramide-monohexoside, are related to hepatic I/R injury and provide a new perspective in understanding the mechanisms responsible for hepatic I/R injury.