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.
Chin Med J (Engl). 2009 Dec 20;122(24):3025-31.
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.
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).
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.
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.
肝缺血再灌注（I/R）损伤发生在许多临床操作中。然而，导致肝 I/R 损伤的分子机制尚不清楚。鞘脂类，特别是神经酰胺，在应激和死亡受体诱导的肝细胞死亡中发挥作用，导致几种肝脏疾病的进展，包括肝 I/R 损伤。为了进一步确定鞘脂类在肝 I/R 中的作用，有必要对再灌注后鞘脂类进行系统分析。
我们通过延迟提取基质辅助激光解吸电离飞行时间质谱（DE MALDI-TOF-MS）研究了热肝 I/R 损伤大鼠模型中鞘脂类的脂质组学变化。
与对照组相比，再灌注后 1 小时（P < 0.05）和 6 小时（P < 0.01），鞘氨醇和神经鞘磷脂的总量以及大多数鞘脂类的强度明显增加，主要是神经鞘磷脂。再灌注后 6 小时出现 6 种新型神经酰胺和神经鞘磷脂，其质荷比（m/z）分别为 537.8、555.7、567.7、583.8、683.5 和 731.4。再灌注后神经酰胺单己糖苷（m/z）804.4（CMH（d18：1C22：1+Na）（+））也增加，与再灌注后肝损伤程度相关。
三种主要的鞘脂类，神经酰胺、神经鞘磷脂和神经酰胺单己糖苷，与肝 I/R 损伤有关，为理解肝 I/R 损伤的机制提供了新的视角。
