Glutathione metabolism in sepsis
Glutathione metabolism in sepsis
复制标题
DOI：
10.1097/01.ccm.0000278913.19123.13
复制
发表时间：
2007-09-01
影响因子：
8.8
通讯作者：
De Cicco, Marcello
中科院分区：
文献类型：
--
作者：
Biolo, Gianni;Antonione, Raffaella;De Cicco, Marcello
脓毒症的特点是严重的氧化还原失衡。谷胱甘肽在细胞防御氧化和亚硝化应激中发挥着重要作用。关于人类败血症中谷胱甘肽合成反应的信息有限。本综述提出对脓毒症中影响谷胱甘肽合成的潜在因素的现有数据进行批判性分析。谷胱甘肽由其组成氨基酸——谷氨酸、半胱氨酸和甘氨酸合成。半胱氨酸的可用性和谷氨酸半胱氨酸连接酶的活性是谷胱甘肽合成的限速因素。在实验性败血症的急性期，肝脏和其他组织的谷胱甘肽合成能力增加。脓毒症中谷氨酸半胱氨酸连接酶激活的潜在机制涉及还原型/氧化型谷胱甘肽比例降低以及活性氧、一氧化氮、促炎细胞因子、热休克蛋白和身体不活动的影响。半胱氨酸耗竭、蛋白质能量营养不良、高血糖、药理剂量的糖皮质激素以及垂体前叶激素（生长激素、促甲状腺激素、促性腺激素）分泌减少可能会损害谷胱甘肽的合成，这在长期危重疾病中经常观察到。 （Crit Care Med 2007；35[增刊]：S591-S595）
Sepsis is characterized by severe redox imbalance. Glutathione plays a major role in cellular defenses against oxidative and nitrosative stress. There is limited information on the response of glutathione synthesis in human sepsis. This review proposes a critical analysis of available data on potential factors affecting glutathione synthesis in sepsis. Glutathione is synthesized from its constituent amino acids-glutamate, cysteine, and glycine. Cysteine availability and the activity of the enzyme glutamate cysteine ligase are rate-limiting for glutathione synthesis. Glutathione synthetic capacity is increased in liver and other tissues during the acute phase of experimental sepsis. Potential mechanisms for glutamate cysteine ligase activation in sepsis involve a decreased ratio of reduced/oxidized glutathione as well as the effects of reactive oxygen species, nitric oxide species, proinflammatory cytokines, heat shock proteins, and physical inactivity. Glutathione synthesis can be impaired by cysteine depletion, protein-energy malnutrition, hyperglycemia, glucocorticoid at pharmacologic doses, and decreased secretion of anterior pituitary hormones (growth hormones, thyrotropin, gonadotropins), as often observed in prolonged critical illness. (Crit Care Med 2007; 35[Suppl.]: S591-S595)