Tazuke Yuko, Drongowski Robert A, Btaiche Imad, Coran Arnold G, Teitelbaum Daniel H
Section of Pediatric Surgery, Department of Surgery, University of Michigan Medical School, F3970 Mott Children's Hospital, Ann Arbor, MI 48109-0245, USA.
Pediatr Surg Int. 2004 Apr;20(4):224-8. doi: 10.1007/s00383-003-1115-1. Epub 2004 Mar 18.
Lipids are an important component of total parenteral nutrition (TPN), contributing the largest caloric load per volume of solution and providing essential fatty acids necessary for survival. However, lipids are known to be causative factors in oxidative stress, which are expressed via the Bcl-2 family of proteins and/or Fas-mediated apoptosis in several tissues. Interestingly, we have recently observed an increase in hepatocyte apoptosis with administration of TPN. To address the mechanism of this apoptosis, we investigated the effects of parenteral lipid administration on apoptotic signaling in a mouse model. C57BL/6J male mice received physiologic saline and standard chow (control) or standard TPN solution with (TPN+L) or without lipid (TPN-L) emulsion. After 7 days of infusion, apoptosis increased in the TPN+L at a significantly higher rate compared with control and TPN-L groups ( p<0.05). Both TPN, with and without lipids, suppressed the pro-apoptotic signals Bid and Bcl-xs ( p<0.05). In contrast, TPN with lipid increased the expression of Fas and both the pro-apoptotic factor Bad and the anti-apoptotic factor Bcl-xl ( p<0.05). These changes may contribute to TPN-induced hepatocyte injury (apoptosis) or suppress the ability of liver hepatocytes to regenerate.
脂质是全胃肠外营养（TPN）的重要组成部分，每单位体积溶液中所含热量最高，并提供生存所需的必需脂肪酸。然而，脂质是氧化应激的致病因素，可通过Bcl-2蛋白家族和/或Fas介导的凋亡在多个组织中表现出来。有趣的是，我们最近观察到给予TPN后肝细胞凋亡增加。为了探究这种凋亡的机制，我们在小鼠模型中研究了胃肠外给予脂质对凋亡信号传导的影响。C57BL/6J雄性小鼠接受生理盐水和标准饲料（对照组）或含脂质（TPN+L）或不含脂质（TPN-L）乳剂的标准TPN溶液。输注7天后，与对照组和TPN-L组相比，TPN+L组的凋亡率显著升高（p<0.05）。含脂质和不含脂质的TPN均抑制了促凋亡信号Bid和Bcl-xs（p<0.05）。相反，含脂质的TPN增加了Fas、促凋亡因子Bad和抗凋亡因子Bcl-xl的表达（p<0.05）。这些变化可能导致TPN诱导的肝细胞损伤（凋亡）或抑制肝肝细胞的再生能力。
