Laboratory of Biochemical Investigations (LIBIM), School of Medicine, National Northeastern University (UNNE), IQUIBA-NEA CONICET, Corrientes, Argentina.
Pharmacology, Faculty of Biochemical and Pharmaceutical Sciences, National University of Rosario (UNR), CONICET, Rosario, Argentina.
Biomed Pharmacother. 2018 Nov;107:1046-1055. doi: 10.1016/j.biopha.2018.08.087. Epub 2018 Aug 25.
Acute kidney injury (AKI) is a frequent complication of sepsis, with a high mortality. Hallmarks of septic-AKI include inflammation, endothelial injury, and tissue hypoxia. Therefore, it would be of interest to develop therapeutic approaches for improving the microvascular damage in septic-AKI. Erythropoietin (EPO) is a well-known cytoprotective multifunctional hormone. Thus, the aim of this study was to evaluate the protective effects of EPO on microvascular injury in a murine model of endotoxemic AKI. Male Balb/c mice were divided into four groups: control, LPS (8 mg/kg, ip.), EPO (3000 IU / kg, sc.) and LPS + EPO. A time course study (0-48 h) was designed. Experiments include, among others, immunohistochemistry and Western blottings of hypoxia-inducible transcription factor (HIF-1α), erythropoietin receptor (EPO-R), vascular endothelial growth factor system (VEGF/VEGFR-2), platelet and endothelial adhesion molecule-1 (PeCAM-1), inducible nitric oxide synthase (iNOS) and phosphorylated nuclear factor kappa B p65 (NF-κB). Data showed that EPO attenuates renal microvascular damage during septic-AKI progression through a) the decrease of HIF-1 alpha, iNOS, and NF-κB and b) the enhancement of EPO-R, PeCAM-1, VEGF, and VEGFR-2 expression. In summary, EPO renoprotection involves the attenuation of septic-induced renal hypoxia and inflammation as well as ameliorates the endotoxemic microvascular injury.
急性肾损伤（AKI）是脓毒症的常见并发症，死亡率很高。脓毒症性 AKI 的特征包括炎症、内皮损伤和组织缺氧。因此，开发改善脓毒症性 AKI 微血管损伤的治疗方法将是非常有意义的。促红细胞生成素（EPO）是一种众所周知的细胞保护多功能激素。因此，本研究旨在评估 EPO 对内毒素性 AKI 小鼠模型中微血管损伤的保护作用。雄性 Balb/c 小鼠分为四组：对照组、LPS（8mg/kg，腹腔注射）、EPO（3000IU/kg，皮下注射）和 LPS+EPO。设计了一个时间过程研究（0-48 小时）。实验包括免疫组织化学和 Western blot 检测缺氧诱导转录因子（HIF-1α）、促红细胞生成素受体（EPO-R）、血管内皮生长因子系统（VEGF/VEGFR-2）、血小板和内皮细胞黏附分子-1（PeCAM-1）、诱导型一氧化氮合酶（iNOS）和磷酸化核因子 kappa B p65（NF-κB）。结果表明，EPO 通过以下两种方式减轻脓毒症性 AKI 进展过程中的肾脏微血管损伤：a）降低 HIF-1α、iNOS 和 NF-κB；b）增强 EPO-R、PeCAM-1、VEGF 和 VEGFR-2 的表达。总之，EPO 的肾保护作用涉及减轻脓毒症引起的肾脏缺氧和炎症，并改善内毒素性微血管损伤。
