Departamento de Cirurgia, Centro de Cirurgia Experimental, Programa de Pós-Graduação em Ciências Cirúrgicas, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratório de Biologia Redox do Instituto de Ciências Biomédicas da UFRJ, Brazil.
J Surg Res. 2021 Jun;262:212-223. doi: 10.1016/j.jss.2021.01.014. Epub 2021 Feb 18.
Intestinal ischemia-reperfusion (I/R) injury constitutes a severe disorder, in great part resulting from oxidative stress. Because sulforaphane and albumin were shown to increase antioxidant defenses, we evaluated the therapeutic potential of these agents in an experimental model of I/R injury.
Wistar rats were used to establish a model of intestinal I/R (35 min of ischemia, followed by 45 min of reperfusion) and were treated with albumin (5 mL/kg), sulforaphane (500 μg/kg), or saline intravenously before reperfusion. Animals that were not subjected to I/R served as the sham (laparotomy only) and control groups. Blood samples were analyzed for arterial gas, reactive oxygen species, and reactive nitrogen species using different molecular fluorescent probes. After euthanasia, ileal samples were collected for analysis, including histopathology, immunohistochemistry, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling assays, and lactic dehydrogenase measurement.
Oxygenation status and hemodynamic parameters were uniform during the experiment. The sulforaphane- or albumin-treated groups showed reduced concentrations of reactive oxygen species (P < 0.04), nitric oxide (P < 0.001), and peroxynitrite (P = 0.001), compared with I/R injury untreated animals. Treatment with sulforaphane or albumin resulted in the preservation of goblet cells (P < 0.03), reductions in histopathologic scores (P < 0.01), macrophage density (P < 0.01), iNOS expression (P < 0.004), NF-kappa B activation (P < 0.05), and apoptotic rates (P < 0.04) in the mucosa and a reduction in the concentration of lactic dehydrogenase (P < 0.04), more pronounced with sulforaphane.
Attenuation of intestinal I/R injury in this model probably reflects the antioxidative effects of systemic administration of both sulforaphane and albumin and reinforces their use in future translational research.
肠缺血再灌注（I/R）损伤构成了一种严重的疾病，在很大程度上是由于氧化应激引起的。由于萝卜硫素和白蛋白被证明可以增加抗氧化防御，我们评估了这些药物在 I/R 损伤实验模型中的治疗潜力。
使用 Wistar 大鼠建立肠 I/R 模型（缺血 35 分钟，再灌注 45 分钟），并在再灌注前静脉注射白蛋白（5ml/kg）、萝卜硫素（500μg/kg）或生理盐水。未发生 I/R 的动物作为假手术（仅剖腹手术）和对照组。使用不同的分子荧光探针分析动脉血气、活性氧和活性氮物种。安乐死后，收集回肠样本进行分析，包括组织病理学、免疫组织化学、末端脱氧核苷酸转移酶（TdT）介导的 dUTP 缺口末端标记测定和乳酸脱氢酶测定。
实验过程中氧合状态和血流动力学参数保持一致。与未治疗的 I/R 损伤动物相比，萝卜硫素或白蛋白治疗组的活性氧（P<0.04）、一氧化氮（P<0.001）和过氧亚硝酸盐（P=0.001）浓度降低。萝卜硫素或白蛋白治疗可保存杯状细胞（P<0.03），降低组织病理学评分（P<0.01）、巨噬细胞密度（P<0.01）、iNOS 表达（P<0.004）、NF-κB 激活（P<0.05）和粘膜细胞凋亡率（P<0.04），并降低乳酸脱氢酶浓度（P<0.04），萝卜硫素作用更明显。
在该模型中，肠 I/R 损伤的减轻可能反映了全身给予萝卜硫素和白蛋白的抗氧化作用，并加强了它们在未来转化研究中的应用。
