Circulating and muscle glutathione turnover in human endotoxaemia
Circulating and muscle glutathione turnover in human endotoxaemia
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DOI：
10.1042/cs20080462
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发表时间：
2009-11-01
期刊：
影响因子：
6
通讯作者：
Rooyackers, Olav E.
中科院分区：
文献类型：
--
作者：
Flaring, Urban B.;Hebert, Christina;Rooyackers, Olav E.
感染性休克患者血浆谷胱甘肽浓度较高，而红细胞和肌肉细胞内谷胱甘肽浓度较低。在本研究中，我们使用人类内毒素模型研究了脓毒症初期健康志愿者体内谷胱甘肽状态和谷胱甘肽动力学的时间模式。本研究是对健康男性志愿者(n=8)内毒素攻击前后的描述性先导性研究。静脉注射内毒素后4h测定血浆和全血谷胱甘肽含量，内毒素注射后2、4h测定骨骼肌谷胱甘肽含量。血浆中总谷胱甘肽浓度在内毒素攻击后3h下降24%(P<；0.001)，4h下降32%(P<；005)，全血和骨骼肌中谷胱甘肽和总谷胱甘肽浓度以及氧化还原状态在内毒素攻击后最初4h内保持不变。全血谷胱甘肽合成率分别为38+/-20%/d和59+/-22%/d(P=0.088)，骨骼肌分别为41+/-25%和46+/-18%(P=0.68)。在脓毒症的初始阶段，以静脉注射内毒素攻击健康志愿者为代表，血浆总谷胱甘肽浓度下降，而骨骼肌和全血中的谷胱甘肽状态和合成速率保持不变。然而，由于合成测量的差异，需要更大的研究来证实这些发现。
Patients with septic shock have high plasma glutathione concentrations, whereas intracellular concentrations in erythrocytes and muscle are low. In the present study, we investigated the temporal pattern of glutathione status and glutathione kinetics in healthy volunteers during the initial phase of sepsis using a human endotoxin model. The present study was a descriptive pilot study in healthy male volunteers (n = 8) before and after an endotoxin challenge. The glutathione status was determined in plasma and whole blood at baseline and hourly for 4 h after intravenous endotoxin injection and in skeletal muscle at baseline and at 2 and 4 h after endotoxin injection. In plasma, the concentration of total glutathione decreased 24% (P < 0.05) at 3 h after endotoxin injection and 32 % (P < 0.001) at 4 h. In whole blood and skeletal muscle, the concentrations of both GSH and total glutathione as well as the redox status remained unaltered during the initial 4 h after the endotoxin challenge. The FSR (fractional synthesis rate) of glutathione in whole blood was 38 +/- 20 %/day before and 59 +/- 22 %/day 4 h after the endotoxin challenge (P = 0.088) and in skeletal muscle this was 41 +/- 25 and 46 +/- 18 %/day (P = 0.68) respectively. During the initial phase of sepsis, as represented by an intravenous endotoxin challenge to healthy volunteers, plasma concentrations of total glutathione decreased, whereas glutathione status and synthesis rate in skeletal muscle and whole blood remained unaltered. However, due to the variation in the synthesis measurements, larger studies are needed to confirm these findings.