The changes of sphingolipid profiles post ischemia–reperfusion injury in the rat liver

Hepatic ischemia-reperfusion (I/R) injury occurs in many clinical procedures, including liver transplantation, hepatic trauma, and liver resection. The molecular mechanisms responsible for hepatic I/R damage however remain unknown. There is increasing evidence that sphingholipids, 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. In the present study, 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 spingolipids, mainly sphingomyelin, significantly increased 1 hr post-reperfusion (p<0.05) and reached peaks at 6 hrs post-reperfusion (p<0.01) compared to controls. Six new forms of ceramide and sphingomyelins appeared 6 hrs post-reperfusion, (m/z) 537.8, 555.7, 567.7, 583.8, 683.5, 731.4. Interestingly, a ceramide- monohexoside (m/z) 804.4 (CMH[d18:1C22:1+Na]+) also increased post-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 mechanism(s) responsible for hepatic I/R injury.     

Notch3在大鼠肝癌中的表达及其意义

目的 研究Notch3在大鼠肝癌发生发展中的动态变化.方法 二乙基亚硝胺诱导大鼠肝细胞癌的发生,于4周、8周、12周、16周时取肝脏标本,免疫组化和Western blot法检测标本中Notch3的表达.结果 随着肝组织损伤加剧,Notch3表达逐渐升高.与正常组相比,肝损伤组、肝硬化组和肝癌组的Notch3蛋白明显表达增加(P＜0.05).结论 Notch3参与了大鼠肝癌发生的全过程,并且随着肝损伤的不断加剧,其表达也逐渐上升.Notch3信号的激活可能是肝癌发生的一项重要机制.     

鞘脂在肝脏疾病中的作用研究进展

随着基因组学和蛋白组学的发展，近年来出现了脂类组学，即研究一个生物体内所有的脂类分子的特性，以及它们在蛋白质表达和基因表达调节过程中的作用^[1]。鞘脂（sphingolipids，SLs）是脂类重要的组成部分，其性质非常活跃。自Thudichum在1884年首次从脑组织中分离得到SLs以来，它就作为真核细胞膜上的结构成分为我们所熟知。