Boudjema K, Southard J H, Belzer F O, Jaeck D, Cinqualbre J
Unité de transplantation d'organes et laboratoire de chirurgie expérimentale, Hôpital de Hautepierre, Strasbourg.
Chirurgie. 1991;117(9):675-82.
A loss of glutathione (GT) from the kidney can cause increased sensitivity to oxygen free radical-induced injury. In this study we investigated the effects of kidney preservation on GT concentration in the cortex tissue, and how various GT precursors affect GT concentration in the dog kidney. During five day continuous machine perfusion of the kidney at 5 degrees C, there was a loss of GT from the cortex tissue (524 +/- 1% GT remained after 5 days). Perfusion with reduced glutathione (GSH, 3 mM) suppressed this loss (77 +/- 11% of GT remained after 5 days). Oxidized glutathione (GSSG) did not prevent the loss of GT. The addition of the three amino acids that make up GT (glycine, glutamic acid, and cysteine, 3 mM each) stimulated the synthesis of GT in the kidney during hypothermic perfusion (137 +/- 23% of control values at 5 days). The increase in tissue GT stimulated by GSH or other precursors was sensitive to the GT synthetase inhibitor, buthionine sulfoximine. This indicated active GT metabolism even at 5 degrees C in perfused kidneys. This study showed that in kidney preservation there was a loss of GT that could be suppressed by the addition of various precursors for GT synthesis. The loss of GT from preserved kidneys may be one cause of post-transplant renal injury which could be prevented by utilization of the appropriate GT precursors.
肾脏中谷胱甘肽（GT）的丧失会导致对氧自由基诱导损伤的敏感性增加。在本研究中，我们调查了肾脏保存对皮质组织中GT浓度的影响，以及各种GT前体如何影响犬肾中的GT浓度。在5℃下对肾脏进行为期五天的连续机器灌注期间，皮质组织中的GT有所丧失（5天后仍保留524±1%的GT）。用还原型谷胱甘肽（GSH，3 mM）灌注可抑制这种丧失（5天后仍保留77±11%的GT）。氧化型谷胱甘肽（GSSG）不能防止GT的丧失。添加构成GT的三种氨基酸（甘氨酸、谷氨酸和半胱氨酸，各3 mM）在低温灌注期间刺激了肾脏中GT的合成（5天时为对照值的137±23%）。由GSH或其他前体刺激的组织GT增加对GT合成酶抑制剂丁硫氨酸亚砜胺敏感。这表明即使在5℃下灌注的肾脏中也存在活跃的GT代谢。本研究表明，在肾脏保存过程中存在GT的丧失，添加各种GT合成前体可抑制这种丧失。保存肾脏中GT的丧失可能是移植后肾损伤的一个原因，利用适当的GT前体可以预防这种损伤。
