Department of Infectious Diseases, Faculty of Health Sciences, University of Copenhagen, The Centre of Inflammation and Metabolism, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark.
Crit Care. 2009;13(1):R7. doi: 10.1186/cc7696. Epub 2009 Jan 27.
Glutamine supplementation has beneficial effects on morbidity and mortality in critically ill patients, possibly in part through an attenuation of the proinflammatory cytokine response and a stimulation of heat shock protein (HSP)70. We infused either alanine-glutamine or saline during endotoxin challenge and measured plasma cytokines and HSP70 protein expression.
This crossover study, conducted in eight healthy young men, was double-blind, randomized and placebo-controlled. It was performed on 2 trial days, separated by a 4-week washout period. The volunteers received an infusion of alanine-glutamine at a rate of 0.025 g/(kg body weight x hour) or saline for 10 hours. After 2 hours, an intravenous bolus of Escherichia coli endotoxin (0.3 ng/kg) was administered. Blood samples were collected hourly for the following 8 hours. HSP70 protein content in isolated blood mononuclear cells (BMNCs) was measured by Western blotting.
Plasma glutamine increased during alanine-glutamine infusion. Endotoxin reduced plasma glutamine during both trials, but plasma glutamine levels remained above baseline with alanine-glutamine supplementation. Endotoxin injection was associated with alterations in white blood cell and differential counts, tumour necrosis factor-alpha, IL-6, temperature and heart rate, but glutamine affected neither the endotoxin-induced change in these variables nor the expression of HSP70 in BMNCs.
Endotoxin reduced plasma glutamine independently of alanine-glutamine infusion, but supplementation allows plasma levels to be maintained above baseline. Glutamine alters neither endotoxin-induced systemic inflammation nor early expression of HSP70 in BMNCs.
ClinicalTrials.gov ID: NCT 00780520.
谷氨酰胺补充对危重症患者的发病率和死亡率有有益影响,这可能部分是通过减轻促炎细胞因子反应和刺激热休克蛋白 (HSP)70 实现的。我们在脂多糖(内毒素)刺激期间输注丙氨酰-谷氨酰胺或生理盐水,并测量血浆细胞因子和 HSP70 蛋白表达。
这项在 8 名健康年轻男性中进行的交叉研究为双盲、随机和安慰剂对照研究。它在 2 个试验日进行,间隔 4 周洗脱期。志愿者接受丙氨酰-谷氨酰胺输注,速度为 0.025 g/(kg 体重 x 小时)或生理盐水输注 10 小时。2 小时后,静脉注射大肠杆菌内毒素(0.3 ng/kg)。接下来的 8 小时内,每小时采集一次血样。通过 Western 印迹法测量分离的血单核细胞(BMNC)中的 HSP70 蛋白含量。
丙氨酰-谷氨酰胺输注期间血浆谷氨酰胺增加。在两次试验中,内毒素均降低了血浆谷氨酰胺,但在补充丙氨酰-谷氨酰胺后,血浆谷氨酰胺水平仍保持在基线以上。内毒素注射与白细胞和分类计数、肿瘤坏死因子-α、IL-6、体温和心率的变化有关,但谷氨酰胺既不影响这些变量的内毒素诱导变化,也不影响 BMNCs 中 HSP70 的表达。
内毒素独立于丙氨酰-谷氨酰胺输注降低了血浆谷氨酰胺,但补充使血浆水平保持在基线以上。谷氨酰胺既不改变内毒素诱导的全身炎症反应,也不改变 BMNCs 中 HSP70 的早期表达。
ClinicalTrials.gov ID:NCT 00780520。