Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Shock. 2010 Mar;33(3):322-31. doi: 10.1097/SHK.0b013e3181b38ef6.
This study describes increased sarcolemmal permeability and myofilamentar damage that occur together with lipid peroxidation and protein nitration in the myocardium in severe sepsis induced by cecal ligation and puncture. Male C57BL/6 mice were submitted to moderate and severe septic injury and sham operation. Using light and laser confocal microscopy, diffuse foci of myocytolysis associated with focal disruption of the actin/myosin contractile apparatus could be seen in hearts with severe septic injury. The myocardial expressions of the sarcomeric proteins myosin and actin were downregulated by both severe and moderate injuries. The detection of albumin staining in the cytoplasm of myocytes to evaluate sarcolemmal permeability provided evidence of severe and mild injury of the plasma membrane in hearts with severe and moderate septic injury, respectively. The administration of a superoxide scavenger caused marked reduction of sarcolemmal permeability, indicating the involvement of free radicals in its genesis. On electron microscopy, these changes were seen to correspond to spread blocks of a few myocytes with fragmentation and dissolution of myofibrils, intracellular edema, and, occasionally, rupture of the sarcolemma. In addition, oxidative damage to lipids, using anti-4-hydroxynonenal, an indicator of oxidative stress and disruption of plasma membrane lipids, and to proteins, using antinitrotyrosine, a stable biomarker of peroxynitrite-mediated protein nitration, was demonstrated. These findings make plausible the hypothesis that increased sarcolemmal permeability might be a primary event in myocardial injury in severe sepsis possibly due to oxidative damage to lipids and proteins that could precede phenotypic changes that characterize a septic cardiomyopathy.
本研究描述了在盲肠结扎和穿刺诱导的严重脓毒症中，心肌发生的肌浆膜通透性增加和肌丝损伤，同时伴有脂质过氧化和蛋白质硝化。雄性 C57BL/6 小鼠接受中度和重度脓毒症损伤和假手术。使用光镜和激光共聚焦显微镜，可以在严重脓毒症损伤的心脏中看到与肌球蛋白/肌动蛋白收缩装置局灶性破坏相关的弥散性肌溶解焦点。严重和中度损伤均可下调肌节蛋白肌球蛋白和肌动蛋白的心肌表达。用细胞质中白蛋白染色来评估肌浆膜通透性，为严重和中度脓毒症损伤的心脏提供了细胞膜严重和轻度损伤的证据。超氧化物清除剂的给药导致肌浆膜通透性明显降低，表明自由基参与了其发生。在电子显微镜下，这些变化与少数肌细胞的扩展块相对应，这些肌细胞的肌原纤维碎裂和溶解、细胞内水肿，偶尔还有肌浆膜破裂。此外，使用抗 4-羟壬烯醛（一种氧化应激和质膜脂质破坏的指标）检测脂质氧化损伤，以及使用抗硝基酪氨酸（一种过氧亚硝酸盐介导的蛋白质硝化的稳定生物标志物）检测蛋白质氧化损伤，证明了这一点。这些发现使肌浆膜通透性增加可能是严重脓毒症中心肌损伤的一个主要事件的假说变得合理，这可能是由于脂质和蛋白质的氧化损伤，这可能先于特征为脓毒症性心肌病的表型变化。
