Klinik und Poliklinik für Anästhesiologie, University of Würzburg, Würzburg, Germany.
Microcirculation. 2010 Oct;17(7):504-13. doi: 10.1111/j.1549-8719.2010.00044.x.
Reactive oxygen species (ROS) are important in the hepatocellular injury process during a systemic inflammation. We examined the role of carbon monoxide (CO) on the hepatic generation of ROS with in-vivo and in-vitro models of systemic inflammation.
Using a murine model of bilateral hindlimb ischemia-reperfusion (I/R) we examined the effect of CO treatment on hepatic ROS formation, oxidative status, and cell injury. Cultured HUVEC were used to investigate intracellular pathways.
CO treatment reduced hepatic lipid peroxidation, re-established total hepatic glutathione and glutathione disulfide (GSH/GSSG) levels and reduced hepatocellular injury. Inhibition of heme oxygenase (HO) during treatment with CO during hindlimb I/R failed to alter the antioxidant qualities provided by CO. The production of ROS after tumor necrosis factor-α (TNF-α) stimulation in HUVEC was diminished after exposure to CO. Treatment with CO during HO inhibition reduced both ROS formation and cell injury. Inhibiting the p38 MAPK (mitogen-activated protein kinase) pathway with pyridinyl imidazol (SB203580) revealed that the antioxidant potential of CO involved the activation of p38 MAPK.
CO has direct antioxidant potential independently of any HO activity during systemic inflammation. The antioxidant effects afforded by CO involve the activation of the p38 MAPK pathway.
活性氧（ROS）在全身炎症过程中的肝细胞损伤中起重要作用。我们通过全身炎症的体内和体外模型研究了一氧化碳（CO）对肝内 ROS 生成的作用。
我们使用双侧后肢缺血再灌注（I/R）的小鼠模型，研究了 CO 处理对肝 ROS 形成、氧化状态和细胞损伤的影响。培养的 HUVEC 用于研究细胞内途径。
CO 处理可降低肝脂质过氧化、重建总肝谷胱甘肽和谷胱甘肽二硫化物（GSH/GSSG）水平，并减少肝细胞损伤。在 hindlimb I/R 期间用 CO 治疗时抑制血红素加氧酶（HO），不能改变 CO 提供的抗氧化特性。CO 暴露后，HUVEC 中肿瘤坏死因子-α（TNF-α）刺激后 ROS 的产生减少。HO 抑制期间用 CO 处理可减少 ROS 形成和细胞损伤。用嘧啶基咪唑（SB203580）抑制 p38 MAPK（丝裂原激活蛋白激酶）途径表明，CO 的抗氧化潜力涉及 p38 MAPK 的激活。
在全身炎症期间，CO 具有独立于任何 HO 活性的直接抗氧化潜力。CO 提供的抗氧化作用涉及 p38 MAPK 途径的激活。
