den Butter G, Lindell S L, Sumimoto R, Schilling M K, Southard J H, Belzer F O
Department of Surgery, University of Wisconsin, Madison 53792.
Transplantation. 1993 Oct;56(4):817-22. doi: 10.1097/00007890-199310000-00007.
Glycine has been shown to protect renal tubule cells and hepatocytes from ischemia, ATP depletion, and cold storage injury. Glycine may be a useful additive to organ preservation solutions or suppress reperfusion injury by infusion into recipients of liver transplantation. In this study, the effects of glycine on survival and postoperative liver injury were studied in the rat and dog orthotopic transplant model. Rat livers preserved for 30 hr in the University of Wisconsin (UW) solution were 50% viable (3 of 6 survivors for 7 days). When glutathione was replaced by 10 mM glycine, survival increased to 100% (6 of 6). There was a significant reduction in hepatocellular injury at the end of preservation (lactate dehydrogenase [LDH] in the pretransplant flush-out of the liver was lower in the glycine group) and after transplantation (serum LDH concentration 6 hr after transplant was lower in the glycine group). In the dog, omission of glutathione from the UW solution resulted in 33% survival (48-hr preservation model) versus 100% survival with glutathione. Replacing glutathione in the UW solution by glycine did not improve survival (33% after 48 hr of preservation). However, when glycine was given to recipients of livers preserved in the UW solution for 24 or 48 hr, there was a decrease in the degree of hepatocellular injury. After 48 hr of preservation, peak aspartate aminotransferase, alanine aminotransferase, and LDH were reduced by about 45-55% when glycine was given to the recipient. Although the differences, with and without glycine treatment of the recipients, did not reach statistical significance, there was a noticeable reduction in hepatocellular injury with glycine. There was 100% survival of dogs in the groups that received livers preserved with the UW solution plus or minus glycine infusion. Hepatamine, a parenteral nutrition solution containing glycine and other amino acids increased hepatocellular injury (higher concentrations of aspartate aminotransferase, alanine transferase, and LDH versus control 48-hr preserved livers), although all dogs survived. This study shows that glycine is cytoprotective when administered to recipients of livers preserved for 24 or 48 hr and suppresses hepatocellular injury, as reflected in a reduction in the concentration of serum enzymes. However, the differences, with and without glycine, were, at best, marginal and further studies are needed to determine whether glycine would make a significant improvement in liver preservation and prevent primary nonfunction.
甘氨酸已被证明可保护肾小管细胞和肝细胞免受缺血、ATP耗竭及冷藏损伤。甘氨酸可能是器官保存液中的一种有用添加剂，或通过输注给肝移植受者来抑制再灌注损伤。在本研究中，在大鼠和犬的原位移植模型中研究了甘氨酸对生存及术后肝损伤的影响。在威斯康星大学（UW）溶液中保存30小时的大鼠肝脏，其存活比例为50%（6只中有3只存活7天）。当用10 mM甘氨酸替代谷胱甘肽时，存活率增至100%（6只全部存活）。保存结束时肝细胞损伤显著减轻（甘氨酸组肝脏移植前冲洗液中的乳酸脱氢酶[LDH]较低），移植后也是如此（甘氨酸组移植后6小时血清LDH浓度较低）。在犬中，UW溶液中省略谷胱甘肽导致存活率为33%（48小时保存模型），而使用谷胱甘肽时存活率为100%。用甘氨酸替代UW溶液中的谷胱甘肽并未提高存活率（保存48小时后为33%）。然而，当给用UW溶液保存24或48小时的肝脏的受者给予甘氨酸时，肝细胞损伤程度有所降低。保存48小时后，当给受者给予甘氨酸时，天冬氨酸转氨酶、丙氨酸转氨酶和LDH的峰值降低了约45 - 55%。尽管接受或未接受甘氨酸治疗的受者之间的差异未达到统计学显著性，但甘氨酸使肝细胞损伤有明显减轻。接受用UW溶液加或不加甘氨酸输注保存的肝脏的犬组存活率为100%。肝胺，一种含有甘氨酸和其他氨基酸的肠外营养溶液，增加了肝细胞损伤（与对照的48小时保存肝脏相比，天冬氨酸转氨酶、丙氨酸转氨酶和LDH浓度更高），尽管所有犬都存活了。本研究表明，当给保存24或48小时的肝脏的受者给予甘氨酸时，它具有细胞保护作用，并抑制肝细胞损伤，这反映在血清酶浓度的降低上。然而，有或没有甘氨酸的差异充其量只是微不足道的，需要进一步研究以确定甘氨酸是否会在肝脏保存方面带来显著改善并预防原发性无功能。
