Departments of Physiology, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Departments of Pathology of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Sci Rep. 2019 May 8;9(1):7090. doi: 10.1038/s41598-019-43564-1.
Glycerol injection in rats can lead to rhabdomyolysis, with the release of the intracellular muscle content to the extracellular compartment and acute kidney injury (AKI). Oxidative stress and the inflammatory processes contribute to the disturbances in renal function and structure observed in this model. This study evaluated the effect of calcitriol administration in AKI induced by rhabdomyolysis and its relationship with oxidative damage and inflammatory process. Male Wistar Hannover rats were treated with calcitriol (6 ng/day) or vehicle (0.9% NaCl) for 7 days and were injected with 50% glycerol or saline 3 days after the beginning of calcitriol or saline administration. Four days after glycerol or saline injection, urine, plasma and renal tissue samples were collected for renal function and structural analysis. The oxidative stress and the inflammatory processes were also evaluated. Glycerol-injected rats presented increased sodium fractional excretion and decreased glomerular filtration rates. These alterations were associated with tubular injury in the renal cortex. These animals also presented increased oxidative damage, apoptosis, inflammation, higher urinary excretion of vitamin D-binding protein and decreased cubilin expression in renal tissue. All these alterations were less intense in calcitriol-treated animals. This effect was associated with decreases in oxidative damage and inflammation.
甘油注射可导致横纹肌溶解,细胞内肌肉内容物释放到细胞外间隙,引起急性肾损伤(AKI)。氧化应激和炎症过程导致该模型中观察到的肾功能和结构紊乱。本研究评估了活性维生素 D 治疗肌红蛋白尿诱导的 AKI 的效果及其与氧化损伤和炎症过程的关系。雄性 Wistar 汉诺威大鼠接受活性维生素 D(6ng/天)或载体(0.9%NaCl)治疗 7 天,并在开始活性维生素 D 或盐水治疗后 3 天注射 50%甘油或盐水。甘油或盐水注射后 4 天,收集尿液、血浆和肾组织样本进行肾功能和结构分析。还评估了氧化应激和炎症过程。甘油注射大鼠的钠分数排泄增加,肾小球滤过率降低。这些改变与肾皮质的肾小管损伤有关。这些动物还表现出氧化损伤、细胞凋亡、炎症增加,尿中维生素 D 结合蛋白排泄增加,肾组织中 cubilin 表达减少。所有这些改变在活性维生素 D 治疗的动物中都不那么剧烈。这种作用与氧化损伤和炎症的减少有关。