Lindell S L, Southard J H, Vreugdenhil P, Belzer F O
Department of Surgery, University of Wisconsin, Madison.
Transplantation. 1994 Oct 27;58(8):869-74. doi: 10.1097/00007890-199410270-00001.
The causes of liver failure after transplantation are multifactorial. An understanding of the mechanisms of injury to the liver could help to define methods to improve preservation and transplantation. We measured protein synthesis by 3H-leucine incorporation into acid precipitable protein in rat liver tissue slices, isolated hepatocytes, and isolated perfused liver (IPL) after cold storage for 24 or 48 hr in University of Wisconsin (UW) solution. Some rats were pretreated with dexamethasone prior to liver harvest. Protein synthesis was depressed in all in vitro models after 24 hr storage. The percent decrease was greater in tissue slices and IPL (about 70% decrease relative to fresh livers) than in isolated hepatocytes (about 30% decrease). Dexamethasone pretreatment improved protein synthesis significantly after 24 hr preservation in tissue slices and in IPL, but had no significant effect on protein synthesis in isolated hepatocytes. The greater loss of protein synthesis in tissue slices and IPL compared with that in isolated hepatocytes was considered in relation to the presence of Kupffer cells in the former systems and lack of Kupffer cells in the isolated cell suspensions. Kupffer cells generate cytotoxins that could cause injury to metabolically depressed hepatocytes or endothelial cells. Dexamethasone has been shown to modulate Kupffer cell inhibition of hepatocyte functions. The results suggest that preservation damage to hepatocytes sensitizes them to further damage on reperfusion by Kupffer cell-generated agents.
移植后肝衰竭的病因是多因素的。了解肝脏损伤机制有助于确定改善肝脏保存和移植的方法。我们在威斯康星大学（UW）溶液中对大鼠肝组织切片、分离的肝细胞和离体灌注肝脏（IPL）进行24或48小时冷保存后，通过将³H-亮氨酸掺入酸沉淀蛋白中来测量蛋白质合成。一些大鼠在肝脏摘取前用 dexamethasone 进行预处理。保存24小时后，所有体外模型中的蛋白质合成均受到抑制。组织切片和IPL中的下降百分比（相对于新鲜肝脏约下降70%）大于分离的肝细胞（约下降30%）。Dexamethasone预处理在组织切片和IPL保存24小时后显著改善了蛋白质合成，但对分离的肝细胞中的蛋白质合成没有显著影响。与分离的肝细胞相比，组织切片和IPL中蛋白质合成的更大损失被认为与前一种系统中存在库普弗细胞以及分离的细胞悬液中缺乏库普弗细胞有关。库普弗细胞产生的细胞毒素可导致代谢受抑制的肝细胞或内皮细胞损伤。已证明dexamethasone可调节库普弗细胞对肝细胞功能的抑制作用。结果表明，对肝细胞的保存损伤使其对库普弗细胞产生的介质再灌注时的进一步损伤敏感。
