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威斯康星大学冷保存液在大鼠肝脏温氧合灌注中的评估:添加果糖可减轻损伤。

Evaluation of University of Wisconsin cold-storage solution in warm hypoxic perfusion of rat liver: the addition of fructose reduces injury.

作者信息

Brass C A, Crawford J M, Narciso J P, Gollan J L

机构信息

Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.

出版信息

Gastroenterology. 1993 Nov;105(5):1455-63. doi: 10.1016/0016-5085(93)90151-2.

Abstract

BACKGROUND

University of Wisconsin cold-storage solution (UW solution) has markedly improved organ preservation for liver transplantation. However, the efficacy of this solution in preserving hepatocyte viability during warm ischemia is undefined; hence, the effects of UW solution on warm hypoxic injury in the isolated perfused rat liver were examined.

METHODS

Livers were perfused using a modified protocol that included a period of hypoxic perfusion with isosmotic Krebs' solution at the end of each experiment. Hepatic injury was evaluated by aspartate aminotransferase (AST) release into the perfusate and the trypan blue perfusion technique.

RESULTS

Although UW solution appeared to decrease hepatic injury during hypoxic perfusion, as reflected by low AST release, perfusion with UW solution led to hepatocyte shrinkage and cessation of bile flow even under oxygenated conditions. UW solution did not protect against warm hypoxic injury, as assessed by AST release into the perfusate (182 +/- 15 U/mL, mean +/- SD) or trypan blue staining of the dead hepatocyte nuclei (56% +/- 5%). However, the addition of fructose to UW solution resulted in a significant decrease in AST release (66 +/- 15 U/mL) and parenchymal cell death (39% +/- 7%).

CONCLUSIONS

These data suggest that the addition of fructose or other gluconeogenic substrates may complement the overall hepatoprotective effects of UW solution, particularly during periods of warm hypoxia.

摘要

背景

威斯康星大学冷保存液(UW液)显著改善了肝移植的器官保存效果。然而,该溶液在热缺血期间保存肝细胞活力的功效尚不清楚;因此,研究了UW液对离体灌注大鼠肝脏热缺氧损伤的影响。

方法

采用改良方案灌注肝脏,该方案在每个实验结束时包括一段用等渗克雷布斯液进行缺氧灌注的时间。通过测定灌注液中天冬氨酸转氨酶(AST)的释放以及台盼蓝灌注技术评估肝损伤。

结果

尽管UW液在缺氧灌注期间似乎能减轻肝损伤,表现为AST释放量低,但即使在有氧条件下,用UW液灌注也会导致肝细胞萎缩和胆汁流动停止。通过测定灌注液中AST的释放量(182±15 U/mL,平均值±标准差)或死亡肝细胞核的台盼蓝染色(56%±5%)评估,UW液不能预防热缺氧损伤。然而,在UW液中添加果糖可显著降低AST的释放量(66±15 U/mL)和实质细胞死亡(39%±7%)。

结论

这些数据表明,添加果糖或其他糖异生底物可能补充UW液的整体肝保护作用,特别是在热缺氧期间。

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