Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Am J Respir Crit Care Med. 2013 Mar 1;187(5):509-17. doi: 10.1164/rccm.201211-1983OC. Epub 2013 Jan 24.
The mechanistic basis for cardiac and renal dysfunction in sepsis is unknown. In particular, the degree and type of cell death is undefined.
To evaluate the degree of sepsis-induced cardiomyocyte and renal tubular cell injury and death.
Light and electron microscopy and immunohistochemical staining for markers of cellular injury and stress, including connexin-43 and kidney-injury-molecule-1 (Kim-1), were used in this study.
Rapid postmortem cardiac and renal harvest was performed in 44 septic patients. Control hearts were obtained from 12 transplant and 13 brain-dead patients. Control kidneys were obtained from 20 trauma patients and eight patients with cancer. Immunohistochemistry demonstrated low levels of apoptotic cardiomyocytes (<1-2 cells per thousand) in septic and control subjects and revealed redistribution of connexin-43 to lateral membranes in sepsis (P < 0.020). Electron microscopy showed hydropic mitochondria only in septic specimens, whereas mitochondrial membrane injury and autophagolysosomes were present equally in control and septic specimens. Control kidneys appeared relatively normal by light microscopy; 3 of 20 specimens showed focal injury in approximately 1% of renal cortical tubules. Conversely, focal acute tubular injury was present in 78% of septic kidneys, occurring in 10.3 ± 9.5% and 32.3 ± 17.8% of corticomedullary-junction tubules by conventional light microscopy and Kim-1 immunostains, respectively (P < 0.01). Electron microscopy revealed increased tubular injury in sepsis, including hydropic mitochondria and increased autophagosomes.
Cell death is rare in sepsis-induced cardiac dysfunction, but cardiomyocyte injury occurs. Renal tubular injury is common in sepsis but presents focally; most renal tubular cells appear normal. The degree of cell injury and death does not account for severity of sepsis-induced organ dysfunction.
败血症导致心肾功能障碍的机制尚不清楚。特别是，细胞死亡的程度和类型尚不清楚。
评估败血症引起的心肌细胞和肾小管细胞损伤和死亡程度。
本研究采用光镜和电镜以及细胞损伤和应激标志物的免疫组织化学染色，包括连接蛋白 43 和肾损伤分子 1（Kim-1）。
在 44 例败血症患者中快速进行了死后心脏和肾脏采集。对照心脏取自 12 例移植和 13 例脑死亡患者。对照肾脏取自 20 例创伤患者和 8 例癌症患者。免疫组织化学显示，败血症和对照组的凋亡心肌细胞水平较低（<1-2 个细胞/千个），并显示败血症中连接蛋白 43 向侧膜重新分布（P < 0.020）。电镜显示仅在败血症标本中出现水肿性线粒体，而线粒体膜损伤和自噬溶酶体在对照组和败血症标本中同样存在。光镜下对照肾脏相对正常；20 例标本中有 3 例约 1%的皮质肾小管出现局灶性损伤。相反，78%的败血症肾脏出现局灶性急性肾小管损伤，常规光镜下和 Kim-1 免疫染色分别在 10.3 ± 9.5%和 32.3 ± 17.8%的皮质-髓质交界处肾小管中出现（P < 0.01）。电镜显示败血症中肾小管损伤增加，包括水肿性线粒体和增加的自噬体。
败血症引起的心脏功能障碍中细胞死亡罕见，但心肌细胞损伤发生。败血症中肾小管损伤常见，但呈局灶性；大多数肾小管细胞看起来正常。细胞损伤和死亡的程度并不能说明败血症引起的器官功能障碍的严重程度。
