Changes of sphingolipids profiles after ischemia-reperfusion injury in the rat liver.
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.
Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.
Shu-Ting
ST
Zhai
Guang-Yi
GY
Liu
Fei
F
Xue
Gong-Ping
GP
Sun
Liang
L
Liang
Wei
W
Chen
Guo-Dong
GD
Xu
Jun-Jian
JJ
Li
Jun
J
Yang
Ting-Bo
TB
Liang
D000818:Animals; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013107:Sphingolipids / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D013107:Sphingolipids; D014409:Tumor Necrosis Factor-alpha