To describe the effect of mechanical ventilation on diaphragm mitochondrial oxygen consumption, ATP production, reactive oxygen species (ROS) generation, and cytochrome c oxidase activity and content, and their relationship to diaphragm strength in an experimental model of sepsis. A cecal ligation and puncture (CLP) protocol was performed in 12 rats while 12 controls underwent sham operation. Half of the rats in each group were paralyzed and mechanically ventilated. We performed blood gas analysis and lactic acid assays 6 h after surgery. Afterwards, we measured diaphragm strength and mitochondrial oxygen consumption, ATP and ROS generation, and cytochrome c oxidase activity. We also measured malondialdehyde (MDA) content as an index of lipid peroxidation, and mRNA expression of the proinflammatory interleukin-1β (IL-1β) in diaphragms. CLP rats showed severe hypotension, metabolic acidosis, and upregulation of diaphragm IL-1β mRNA expression. Compared to sham controls, spontaneously breathing CLP rats showed lower diaphragm force and increased susceptibility to fatigue, along with depressed mitochondrial oxygen consumption and ATP production and cytochrome c oxidase activity. These rats also showed increased mitochondrial ROS generation and MDA content. Mechanical ventilation markedly restored mitochondrial oxygen consumption and ATP production in CLP rats; lowered mitochondrial ROS production by the complex 3; and preserved cytochrome c oxidase activity. In an experimental model of sepsis, early initiation of mechanical ventilation restores diaphragm mitochondrial function.

中文翻译：

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机械通气在大鼠脓毒症模型中保留膈肌线粒体功能


描述脓毒症实验模型中机械通气对膈肌线粒体耗氧量、ATP 产生、活性氧 (ROS) 产生以及细胞色素 C 氧化酶活性和含量的影响，及其与膈肌强度的关系。对 12 只大鼠进行盲肠结扎穿刺 (CLP) 方案，同时对 12 只对照大鼠进行假手术。每组中一半的大鼠处于麻痹状态并进行机械通气。术后 6 小时我们进行了血气分析和乳酸测定。随后，我们测量了膈肌强度和线粒体耗氧量、ATP 和 ROS 生成以及细胞色素 C 氧化酶活性。我们还测量了作为脂质过氧化指标的丙二醛 (MDA) 含量，以及膈肌中促炎白细胞介素 1β (IL-1β) 的 mRNA 表达。 CLP 大鼠表现出严重低血压、代谢性酸中毒和膈肌 IL-1β mRNA 表达上调。与假手术对照组相比，自主呼吸的 CLP 大鼠表现出较低的膈肌力和增加的疲劳敏感性，同时线粒体耗氧量、ATP 产生和细胞色素 C 氧化酶活性降低。这些大鼠还表现出线粒体 ROS 生成和 MDA 含量增加。机械通气显着恢复了 CLP 大鼠的线粒体耗氧量和 ATP 生成；复合物 3 降低了线粒体 ROS 的产生；并保留细胞色素c氧化酶活性。在脓毒症的实验模型中，早期开始机械通气可恢复膈肌线粒体功能。