Stojiljkovic Nenad, Veljkovic Slavimir, Mihailovic Dragan, Stoiljkovic Milan, Radenkovic Mirjana, Rankovic Goran, Randjelovic Pavle
Department of Physiology, University of Nis, School of Medicine, Nis, Serbia.
Ren Fail. 2009;31(1):54-61. doi: 10.1080/08860220802546321.
Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. Thus, the present study was undertaken to determine if pentoxifylline could protect the kidney in this experimental model. Thirty male Wistar rats were used. The animals were divided into three groups, each with 10 animals. The GM group of animals was treated daily with gentamicin in a dose of 100 mg/kg for eight days. The GMP group of animals was treated daily with pentoxifylline in a dose of 45 mg/kg and the same dose of gentamicin as the GM group for eight days. The control group received 1 mL/day saline intraperitoneally. For histological analysis, 5 microm-thick sections were stained with hematoxylin and eosin (HE), periodic acid Schiff (PAS), and Jones methenamine silver. The morphometric parameters included were glomerular area, major and minor axis, perimeter, diameter, roundness, and mean optical density. Biochemical analyses were used to determine concentrations of blood urea, serum creatinine, sodium, and potassium. In the GM group of rats, glomerular basement membrane was diffusely and unequally thickened with polymorphonuclear leukocyte infiltration, and coagulation-type necrosis and vacuolization of cytoplasm of proximal tubules epithelial cells were observed. In the GMP group of rats, glomeruli were slightly enlarged with thickened basement membrane in some segments but without coagulation-type necrosis of proximal tubules epithelial cells. Blood urea and serum creatinine concentration in the GM group were significantly elevated in comparison with the GMP group, while the potassium level was decreased. The present study indicated that pentoxifylline could provide a marked protective effect against gentamicin-induced acute renal failure, most likely mediated by vascular decongestion.
庆大霉素（GM）是一种广泛用于治疗严重及危及生命感染的抗生素，但其效用因肾毒性的产生而受限。因此，本研究旨在确定己酮可可碱在该实验模型中是否能保护肾脏。选用30只雄性Wistar大鼠。将动物分为三组，每组10只。GM组动物每日用100mg/kg剂量的庆大霉素治疗8天。GMP组动物每日用45mg/kg剂量的己酮可可碱及与GM组相同剂量的庆大霉素治疗8天。对照组腹腔注射1mL/天的生理盐水。进行组织学分析时，将5微米厚的切片用苏木精和伊红（HE）、过碘酸希夫（PAS）以及琼斯甲烯胺银染色。所纳入的形态学参数包括肾小球面积、长短轴、周长、直径、圆度以及平均光密度。采用生化分析测定血尿素、血清肌酐、钠和钾的浓度。在GM组大鼠中，肾小球基底膜弥漫性且不均匀增厚，伴有多形核白细胞浸润，可见近端肾小管上皮细胞的凝固型坏死及细胞质空泡化。在GMP组大鼠中，肾小球轻度增大，部分节段基底膜增厚，但未见近端肾小管上皮细胞的凝固型坏死。与GMP组相比，GM组的血尿素和血清肌酐浓度显著升高，而钾水平降低。本研究表明，己酮可可碱对庆大霉素诱导的急性肾衰竭可提供显著的保护作用，其保护作用很可能是通过减轻血管充血介导的。
