Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, 1200, Vienna, Austria.
Inflammation. 2010 Oct;33(5):295-305. doi: 10.1007/s10753-010-9185-4.
The objective of this study was to investigate early effects of peritoneal inflammation on the mitochondrial function in the vital organs, liver and kidney, and their relation to inflammatory and oxidative stress mediators. The study was performed on 14 domestic pigs. Peritoneal inflammation was induced in anesthetized pigs after a midline laparotomy by autologous feces. Fluid resuscitation maintained a MAP above 60 mmHg. Animals were sacrificed 12 h later, and tissue samples were obtained to determine mitochondrial function, mRNA levels of relevant genes [inducible NO synthase (iNOS), inducible HO (HO-1), tumor necrosis factor-alpha (TNF-alpha)], generation of reactive oxygen species (ROS), and HO-1 activity. We found impaired mitochondrial function in both liver and kidney, based on decreased state 3 respiration in the liver and increased states 2 and 4 respiration in the kidney at 12 h. This was accompanied by increased TNF-alpha protein in the blood and up-regulation of TNF-alpha mRNA in the liver. Free iron was elevated in the liver but not in the kidney. In the kidney, mitochondrial ROS production was increased. Nitric oxide levels in blood remained unchanged, corresponding to unchanged levels of iNOS mRNA expression in liver and kidney. Similarly, HO-1 mRNA and heme oxygenase (HO)-activity were unchanged. The inflammatory response in the absence of characteristic septic symptoms was not associated with morphological organ damage at this early time point. Peritoneal inflammation in pigs caused mitochondrial dysfunction in liver and kidney, preceding signs of organ damage. We did not find proof that mitochondrial dysfunction was due to increased levels of either nitric oxide (NO) or products of HO, but it was accompanied by increased levels of oxidative stress markers.
本研究旨在探讨早期腹膜炎症对重要器官（肝脏和肾脏）线粒体功能的影响，及其与炎症和氧化应激介质的关系。研究共纳入 14 头家猪，麻醉后经中腹部切口注入自体粪便以诱发腹膜炎症，液体复苏维持平均动脉压（MAP）大于 60mmHg。12 小时后处死动物，取组织样本以测定线粒体功能、相关基因（诱导型一氧化氮合酶（iNOS）、诱导型血红素氧合酶（HO-1）、肿瘤坏死因子-α（TNF-α））mRNA 水平、活性氧（ROS）生成和 HO-1 活性。我们发现，肝脏的三磷酸腺苷（ATP）合成减少（即状态 3 呼吸降低），肾脏的呼吸增加（即状态 2 和 4 呼吸增加），提示线粒体功能受损，这一结果在 12 小时时可观察到。同时，血液中 TNF-α 蛋白水平升高，肝脏中 TNF-α mRNA 表达上调。肝脏中游离铁增加，但肾脏中没有增加。肾脏中产生的线粒体 ROS 增加。血液中的一氧化氮（NO）水平保持不变，这与肝脏和肾脏中 iNOS mRNA 表达水平不变相对应。类似地，HO-1 mRNA 和血红素加氧酶（HO）活性也没有变化。在没有典型感染症状的情况下，这种炎症反应在早期并未导致器官形态损伤。在本研究中，猪的腹膜炎症导致了肝脏和肾脏的线粒体功能障碍，而器官损伤的迹象发生在此之前。我们没有发现证据表明线粒体功能障碍是由于 NO 或 HO 产物水平升高所致，但它伴随着氧化应激标志物水平的增加。
