Service de Physiologie et d'Explorations Fonctionnelles, Pôle de Pathologie Thoracique, Hôpitaux Universitaires, Centre Hospitalier Régional Universitaire Strasbourg, Strasbourg, France.
Br J Surg. 2011 Apr;98(4):511-6. doi: 10.1002/bjs.7384. Epub 2011 Jan 24.
Cross-clamping of the aorta during abdominal aortic aneurysm surgery induces muscle ischaemia with resultant morbidity. This study tested whether ischaemic postconditioning would decrease mitochondrial dysfunction in skeletal muscle by reducing oxidative stress.
Three groups (9 rats each) underwent surgery, including a control group without ischaemia and an ischaemia-reperfusion group that had 3 h ischaemia induced by aortic clamping and collateral vessel ligation, followed by 2 h of reperfusion. The third group had ischaemia for 3 h then underwent postconditioning comprising three short intervals of ischaemia-reperfusion at the onset of reperfusion. Activity of complexes I, II, III and IV of the mitochondrial respiratory chain was monitored in gastrocnemius muscle, along with oxidative stress measured by dihydroethidium (DHE) staining and antioxidant defence determined by measurement of glutathione levels.
Ischaemia-reperfusion alone caused a significant reduction in maximal oxidative capacity (-31.8 per cent; P = 0.002), activity of complexes II, III and IV (-34.5 per cent; P = 0.007) and complex IV activity (-30.6 per cent; P = 0.039). It also increased reactive oxygen species (DHE staining increased to 223.1 per cent of control value; P = 0.027) and reduced antioxidant defence (glutathione level -28.6 per cent; P = 0.039). Postconditioning counteracted these deleterious effects by increasing mitochondrial complex I, II, III and IV activities, restoring muscle DHE staining and preserving glutathione content.
Ischaemic postconditioning protects skeletal muscle mitochondria against ischaemia-reperfusion injury by reducing oxidative stress and preserving antioxidant defence in an experimental model. Mitochondrial protection to reduce reperfusion injury in clinical vascular surgery may be warranted.
腹主动脉瘤手术中主动脉夹闭会导致肌肉缺血，从而产生相关发病率。本研究通过降低氧化应激来测试缺血后处理是否会减少骨骼肌中的线粒体功能障碍。
三组（每组 9 只大鼠）接受手术，包括无缺血的对照组和缺血再灌注组，该组通过主动脉夹闭和侧支血管结扎诱导 3 小时缺血，然后再灌注 2 小时。第三组缺血 3 小时，然后进行后处理，即在再灌注开始时进行三次短暂的缺血-再灌注间隔。监测比目鱼肌中线粒体呼吸链复合物 I、II、III 和 IV 的活性，通过二氢乙啶（DHE）染色测量氧化应激，通过测量谷胱甘肽水平确定抗氧化防御。
单独的缺血再灌注导致最大氧化能力显著降低（-31.8%；P=0.002），复合物 II、III 和 IV 的活性（-34.5%；P=0.007）和复合物 IV 活性（-30.6%；P=0.039）降低。它还增加了活性氧物种（DHE 染色增加到对照值的 223.1%；P=0.027）并降低了抗氧化防御（谷胱甘肽水平降低了 28.6%；P=0.039）。后处理通过增加线粒体复合物 I、II、III 和 IV 的活性、恢复肌肉 DHE 染色和保持谷胱甘肽含量来抵消这些有害影响。
在实验模型中，缺血后处理通过降低氧化应激和保持抗氧化防御来保护骨骼肌线粒体免受缺血再灌注损伤。在临床血管外科中，可能需要进行线粒体保护以减少再灌注损伤。
