Schuster Heidi, Blanc Marie-Céline, Neveux Nathalie, Bonnefont-Rousselot Dominique, Le Tourneau Agnès, De Bandt Jean-Pascal, Cynober Luc
Laboratoire de Biologie de la Nutrition, EA2498, Faculté de Pharmacie, Université Paris 5, Paris, France.
Scand J Gastroenterol. 2006 Nov;41(11):1342-9. doi: 10.1080/00365520600682039.
Some amino acids (AAs) display potent regulatory activities on cell metabolism, including via anti-oxidative defences. The aim of this study was to evaluate the protective effect of these AAs on warm ischaemia-reperfusion (I/R) injury in the isolated perfused rat liver.
Livers from fasted male Sprague-Dawley rats were isolated and perfused without (control group) or with (AP group) a mixture of regulatory AAs (glutamine, histidine, leucine, methionine, proline, phenylalanine, tryptophan and alanine). After 45 min of perfusion, warm ischaemia was induced for 45 min by clamping the portal vein catheter; thereafter, reperfusion was performed for 30 min.
TNF-alpha production was significantly lower in the AP group during reperfusion (
39+/-7 versus AP: 16+/-2 pg min-1 g-1, p<0.05), and lactate dehydrogenase (LDH) release decreased significantly during the last 15 min of reperfusion (
0.13+/-0.03 versus AP: 0.04+/-0.02 IU min-1 g-1, p<0.05), despite similar levels of oxidative stress. The addition of regulatory AAs was not associated with variations in portal flow, bile flow, hepatic glucose or urea metabolism. However, significant changes in intrahepatic glutamine (
1.4+/-0.2 versus AP: 2.6+/-0.5 micromol g-1, p < 0.05) together with higher glutamate release in the AP group (
10.2+/-5.4 versus AP: 42.6+/-10.9 nmol min-1 g-1, p < 0.05) indicated modifications in nitrogen metabolism.
Taken together, the lower TNF-alpha production, suggesting decreased inflammatory response, the decrease in LDH release in the AP group, demonstrating a better preservation of liver viability, and the increase in hepatic glutamine indicate that AAs play an important role in the liver's response to I/R.
某些氨基酸（AAs）对细胞代谢具有强大的调节活性，包括通过抗氧化防御机制。本研究旨在评估这些氨基酸对离体灌注大鼠肝脏热缺血再灌注（I/R）损伤的保护作用。
从禁食的雄性Sprague-Dawley大鼠分离肝脏，在无调节性氨基酸混合物（对照组）或有调节性氨基酸混合物（AP组）的情况下进行灌注，调节性氨基酸混合物包括谷氨酰胺、组氨酸、亮氨酸、蛋氨酸、脯氨酸、苯丙氨酸、色氨酸和丙氨酸。灌注45分钟后，通过夹闭门静脉导管诱导热缺血45分钟；此后，进行30分钟的再灌注。
再灌注期间，AP组肿瘤坏死因子-α（TNF-α）的产生显著降低（对照组：39±7 对比 AP组：16±2 pg·min⁻¹·g⁻¹，p<0.05），且在再灌注最后15分钟内乳酸脱氢酶（LDH）释放显著减少（对照组：0.13±0.03 对比 AP组：0.04±0.02 IU·min⁻¹·g⁻¹，p<0.05），尽管氧化应激水平相似。添加调节性氨基酸与门静脉血流率、胆汁流量、肝脏葡萄糖或尿素代谢的变化无关。然而，肝内谷氨酰胺有显著变化（对照组：1.4±0.2 对比 AP组：2.6±0.5 μmol·g⁻¹，p<0.05），同时AP组谷氨酸释放增加（对照组：10.2±5.4 对比 AP组：42.6±10.9 nmol·min⁻¹·g⁻¹，p<0.05），这表明氮代谢发生了改变。
综合来看，TNF-α产生降低表明炎症反应减弱，AP组LDH释放减少表明肝脏活力得到更好的保存，肝内谷氨酰胺增加，这表明氨基酸在肝脏对I/R的反应中起重要作用。
