Constantino Larissa, Galant Letícia Selinger, Vuolo Francieli, Guarido Karla Lorena, Kist Luiza Wilges, de Oliveira Giovanna Medeiros Tavares, Pasquali Matheus Augusto de Bittencourt, de Souza Cláudio Teodoro, da Silva-Santos José Eduardo, Bogo Maurício Reis, Moreira José Cláudio Fonseca, Ritter Cristiane, Dal-Pizzol Felipe
Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Avenida Universitária, 1105, 88806-000, Criciúma, SC, Brazil.
Departamento de Farmacologia, Laboratório de Biologia Cardiovascular, Universidade Federal de Santa Catarina, Campus Trindade, CEP 88040-900, Florianópolis, SC, Brazil.
Intensive Care Med Exp. 2017 Dec;5(1):15. doi: 10.1186/s40635-017-0130-9. Epub 2017 Mar 16.
Extracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. However, the profile of ECSOD expression after sepsis is not fully understood. Therefore, we intended to evaluate the content and gene expression of superoxide dismutase (SOD) isoforms in the renal artery and their relation to renal blood flow.
Sepsis was induced in Wistar rats by caecal ligation and perforation. Several times after sepsis induction, renal blood flow (12, 24 and 48 h); the renal arterial content of SOD isoforms, nitrotyrosine, endothelial and inducible nitric oxide synthase (e-NOS and i-NOS), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP); and SOD activity (3, 6 and 12 h) were measured. The influence of a SOD inhibitor was also evaluated.
An increase in ECSOD content was associated with decreased 3-nitrotyrosine levels. These events were associated with an increase in pVASP content and maintenance of renal blood flow. Moreover, previous treatment with a SOD inhibitor increased nitrotyrosine content and reduced renal blood flow.
ECSOD appears to have a major role in decreasing peroxynitrite formation in the renal artery during the early stages of sepsis development, and its application can be important in renal blood flow control and maintenance during septic insult.
细胞外超氧化物歧化酶（ECSOD）通过降低超氧化物水平和防止过氧亚硝酸盐生成来保护一氧化氮（NO）的生物利用度，这对于维持肾血流量和预防急性肾损伤至关重要。然而，脓毒症后ECSOD的表达情况尚未完全明确。因此，我们旨在评估肾动脉中超氧化物歧化酶（SOD）同工型的含量和基因表达及其与肾血流量的关系。
通过盲肠结扎和穿孔诱导Wistar大鼠发生脓毒症。在诱导脓毒症后的几个时间点（12、24和48小时）测量肾血流量；测量肾动脉中SOD同工型、硝基酪氨酸、内皮型和诱导型一氧化氮合酶（e-NOS和i-NOS）以及磷酸化血管舒张刺激磷蛋白（pVASP）的含量；并在诱导后的3、6和12小时测量SOD活性。还评估了SOD抑制剂的影响。
ECSOD含量增加与3-硝基酪氨酸水平降低相关。这些事件与pVASP含量增加和肾血流量维持相关。此外，预先用SOD抑制剂处理会增加硝基酪氨酸含量并降低肾血流量。
在脓毒症发展的早期阶段，ECSOD似乎在减少肾动脉中过氧亚硝酸盐形成方面起主要作用，其应用对于脓毒症损伤期间肾血流量的控制和维持可能很重要。
