Preliminary Research: Application of Non-Invasive Measure of Cytochrome c Oxidase Redox States and Mitochondrial Function in a Porcine Model of Carbon Monoxide Poisoning.
Preliminary Research: Application of Non-Invasive Measure of Cytochrome c Oxidase Redox States and Mitochondrial Function in a Porcine Model of Carbon Monoxide Poisoning.
复制标题
初步研究：细胞色素c氧化酶氧化还原状态和线粒体功能的非侵入性测量在一氧化碳中毒猪模型中的应用。
DOI：
10.1007/s13181-022-00892-5
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Baker,WesleyB
中科院分区：
文献类型：
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作者：
Lewis,Alistair;Forti,RodrigoM;Alomaja,Oladunni;Mesaros,Clementina;Piel,Sarah;Greenwood,JohnC;Talebi,FatimaM;Mavroudis,ConstantineD;Kelly,Matthew;Kao,Shih-Han;Shofer,FrancesS;Ehinger,JohannesK;Kilbaugh,ToddJ;Baker,WesleyB
简介一氧化碳 (CO) 是一种无色无味的气体，是美国环境中毒的主要原因，具有很高的死亡率和发病率。一氧化碳中毒的机制很复杂，包括缺氧、炎症和脑微血管段白细胞隔离导致活性氧增加。另一个重要途径是 CO 对线粒体的影响，特别是细胞色素氧化酶，也称为复合体 IV (CIV)。这项正在进行的研究的目的是初步开发一氧化碳中毒猪模型，以研究脑线粒体生理学的变化。方法将四头猪（10公斤）分为两组：假猪组（n = 2）和二氧化碳组（n = 2）。在 120 分钟内向 CO 组施用 2000 ppm 的 CO 剂量，然后在室内空气中再充氧 30 分钟。对照组接受室内空气 150 分钟。使用非侵入式光学监测来测量 CIV 氧化还原状态。进行脑微透析以获得脑代谢状态的半实时测量。暴露结束后，立即收获新鲜脑组织（皮质和海马）以测量线粒体呼吸。速冻皮质组织也用于 ATP 浓度和蛋白质印迹。结果在一项正在进行的初步研究中，CO 组的动物表现出脑线粒体呼吸、柠檬酸合酶密度、光学测量的 CIV 氧化还原变化可能早期下降，以及乳酸与丙酮酸比率的增加。结论有一个可能可观察到的表型，强调了线粒体功能在 CO 中毒损伤中的重要作用。
IntroductionCarbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochromecoxidase, also known as Complex IV (CIV). The purpose of this ongoing study is the preliminary development of a porcine model of CO poisoning for investigation of alterations in brain mitochondrial physiology.MethodsFour pigs (10 kg) were divided into two groups: Sham (n= 2) and CO (n= 2). Administration of a dose of CO at 2000 ppm to the CO group over 120 minutes followed by 30 minutes of re-oxygenation at room air. The control group received room air for 150 minutes. Non-invasive optical monitoring was used to measure CIV redox states. Cerebral microdialysis was performed to obtain semi real-time measurements of cerebral metabolic status. At the end of the exposure, fresh brain tissue (cortical and hippocampal) was immediately harvested to measure mitochondrial respiration. Snap frozen cortical tissue was also used for ATP concentrations and western blotting.ResultsWhile a preliminary ongoing study, animals in the CO group showed possible early decreases in brain mitochondrial respiration, citrate synthase density, CIV redox changes measured with optics, and an increase in the lactate-to-pyruvate ratio.ConclusionsThere is a possible observable phenotype highlighting the important role of mitochondrial function in the injury of CO poisoning.