Department of Anaesthesiology, University of Duesseldorf, Moorenstrasse 5, 40225, Duesseldorf, Germany.
Department of Anaesthesiology, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands.
Eur J Pharmacol. 2019 Jun 15;853:364-370. doi: 10.1016/j.ejphar.2019.04.031. Epub 2019 Apr 19.
Evidence suggests that propofol infusion syndrome (PRIS) is caused by an altered mitochondrial function. The aim of this study was to examine the effects of propofol and the vehicle MCT on mitochondrial function in hepatic and colonic tissue. Mitochondrial oxygen consumption was determined in colon and liver homogenates after incubation with buffer (control), propofol (50, 75, 100, 500 μM) or the carrier substances DMSO and MCT. State 2 (substrate-dependent) and state 3 (ADP-dependent respiration) were assessed. RCI (respiratory control index) - an indicator for coupling between electron transport chain system (ETS) and oxidative phosphorylation (OXPHOS) and ADP/O ratio - a parameter for efficacy of OXPHOS were calculated. Data were presented as % of control. In hepatic mitochondria, 500 μM propofol reduced RCI formulation-independently (propofol/MCT 500 μM: complex I: 66.3 ± 8.7%, complex II: 75.5 ± 9.2%; propofol/DMSO 500 μM: complex I: 29.1 ± 8.8%, complex II: 49.3 ± 15.5%). 75 μM Propofol/MCT reduced ADP/O for complex I (73.5 ± 27.3%). DMSO did not affect hepatic mitochondria whereas MCT reduced RCI for complex II (87.2 ± 9.8%) and ADP/O for complex I (93.7 ± 31.7%). In colon 50 μM Propofol/MCT increased RCI for complex I and II (complex I: 127.2 ± 10.7%, complex II: 136.8 ± 33.9%) and 100 μM Propofol/MCT for complex I (131.4 ± 18.7%). 500 μM Propofol/DMSO increased ADP/O for complex I (139.4 ± 41.4%). DMSO did not affect RCI but increased ADP/O for both complexes (complex I: 119.9 ± 25.8%, complex II: 110.2 ± 14.2%). MCT increased RCI for complex I (123.0 ± 31.6%). In hepatic mitochondria propofol uncoupled ETS from OXPHOS formulation-independently and propofol/MCT reduced efficacy of OXPHOS. In colonic mitochondria, propofol/MCT strengthened the coupling and propofol/DMSO enhanced the efficacy of OXPHOS.
证据表明，异丙酚输注综合征（PRIS）是由线粒体功能改变引起的。本研究旨在研究异丙酚和载体 MCT 对肝组织和结肠组织中线粒体功能的影响。孵育缓冲液（对照）、异丙酚（50、75、100、500μM）或载体物质 DMSO 和 MCT 后，测定结肠和肝脏匀浆中的线粒体耗氧量。评估状态 2（底物依赖）和状态 3（ADP 依赖呼吸）。计算 RCI（呼吸控制指数）-电子传递链系统（ETS）和氧化磷酸化（OXPHOS）之间偶联的指标，以及 ADP/O 比-OXPHOS 的效力的参数。数据以对照的百分比表示。在肝线粒体中，500μM 异丙酚独立于配方降低 RCI（异丙酚/MCT 500μM：复合物 I：66.3±8.7%，复合物 II：75.5±9.2%；异丙酚/DMSO 500μM：复合物 I：29.1±8.8%，复合物 II：49.3±15.5%）。75μM 异丙酚/MCT 降低了复合物 I 的 ADP/O（73.5±27.3%）。DMSO 对肝线粒体没有影响，而 MCT 降低了复合物 II 的 RCI（87.2±9.8%）和复合物 I 的 ADP/O（93.7±31.7%）。在结肠中，50μM 异丙酚/MCT 增加了复合物 I 和 II 的 RCI（复合物 I：127.2±10.7%，复合物 II：136.8±33.9%），100μM 异丙酚/MCT 增加了复合物 I 的 RCI（131.4±18.7%）。500μM 异丙酚/DMSO 增加了复合物 I 的 ADP/O（139.4±41.4%）。DMSO 没有影响 RCI，但增加了两个复合物的 ADP/O（复合物 I：119.9±25.8%，复合物 II：110.2±14.2%）。MCT 增加了复合物 I 的 RCI（123.0±31.6%）。在肝线粒体中，异丙酚独立于配方使 ETS 与 OXPHOS 解偶联，异丙酚/MCT 降低了 OXPHOS 的效力。在结肠线粒体中，异丙酚/MCT 增强了偶联，异丙酚/DMSO 增强了 OXPHOS 的效力。
