Shriners Burns Hospital and Burn & Trauma Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114 USA.
Shriners Burns Hospital and Burn & Trauma Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114 USA ; Laboratory of Human Nutrition, Massachusetts Institute of Technology, Cambridge, MA, 02142 USA.
Burns Trauma. 2013 Sep 18;1(2):87-94. doi: 10.4103/2321-3868.118934. eCollection 2013.
Previous studies from our laboratories revealed a reduced rate of whole-blood (WB) glutathione (GSH) synthesis in severely burned patients. To determine whether WB GSH metabolism is an indicator of the status of GSH metabolism in one or more of the major organs, we used a burn rabbit model to determine GSH concentrations and rates of synthesis in WB, liver, lungs, kidney, and skeletal muscle. L-[1-(13)C]-cysteine was infused intravenously for 6 h in rabbits at 3 days post-burn and in sham burn controls. WB and organ (13)C-enrichment of cysteine and GSH was determined by gas chromatography/mass spectrometry. Plasma cysteine metabolic flux was increased significantly (P < 0.01) following burn injury. WB, liver, and lung GSH concentrations (P = 0.054, P < 0.05, and P < 0.05, respectively) and fractional rates of GSH synthesis (P < 0.05, P < 0.01, and P < 0.05, respectively) were reduced at 3 days post-burn. Kidney was unaffected. There also appears to be an increased rate of GSH transport out of the liver after burn injury. Hence, there is a differential impact of burn injury on tissue and organ GSH status, with WB qualitatively reflecting the changes in lung and liver. It will be important to determine whether these changes are due to alterations in the intrinsic capacity for GSH synthesis and/or availability of amino acid precursors of GSH.
先前，我们实验室的研究揭示严重烧伤患者全血（WB）谷胱甘肽（GSH）合成率降低。为了确定 WB GSH 代谢是否是一个或多个主要器官 GSH 代谢状态的指标，我们使用烧伤兔模型来确定 WB、肝脏、肺、肾和骨骼肌中的 GSH 浓度和合成率。在烧伤后 3 天和假烧伤对照的兔子中，静脉内输注 L-[1-(13)C]-半胱氨酸 6 小时。通过气相色谱/质谱法测定 WB 和器官（13)C-半胱氨酸和 GSH 的丰度。烧伤后，血浆半胱氨酸代谢通量显著增加（P < 0.01）。WB、肝脏和肺 GSH 浓度（P = 0.054、P < 0.05 和 P < 0.05，分别）和 GSH 合成的分数速率（P < 0.05、P < 0.01 和 P < 0.05，分别）在烧伤后 3 天降低。肾脏不受影响。烧伤后似乎也增加了 GSH 从肝脏转运出的速率。因此，烧伤对组织和器官 GSH 状态的影响存在差异，WB 定性地反映了肺和肝的变化。重要的是要确定这些变化是由于 GSH 合成的内在能力改变还是 GSH 的氨基酸前体的可用性改变所致。
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