Efficacy of darbepoetin in doxorubicin - Induced cardiorenal injury in rats
Efficacy of darbepoetin in doxorubicin - Induced cardiorenal injury in rats
复制标题
DOI：
10.1159/000093258
复制
发表时间：
2006-01-01
影响因子：
--
通讯作者：
Fujita, Toshiro
中科院分区：
文献类型：
--
作者：
Noiri, Eisei;Nagano, Nobuo;Fujita, Toshiro
本研究旨在阐明促红细胞生成素类似物在心肾功能不全综合征使用啮齿动物模型的疗效。用盐酸阿霉素（DXR）诱导肾功能不全。使用较低剂量（3 μ g/kg）和较高剂量（30 μ g/kg）的达贝泊苷α（DA）进行干预。进行肌酐、血尿素氮、铁和血红蛋白的血液检查，直至开始DA给药后11周。在开始DA后10周进行尿液收集，并测定蛋白质、铁和N-乙酰-β-D-氨基葡萄糖苷酶水平以及DA的抗氧化能力。在开始DA给药后11周处死动物时，测量左心室心脏干重。对肾间质纤维化变化和铁沉积进行组织学分析。DA的管理显着改善贫血到正常对照水平，并显着减轻DXR诱导的肌酐，血尿素氮，肾间质纤维化，肾铁沉积，干左心室重量的增加，但血清和尿铁和尿蛋白和N-乙酰-β-D-氨基葡萄糖苷酶水平不变。DA处理动物的尿总自由基捕获抗氧化能力提高到正常对照水平。DA可减轻DXR引起的心肾损伤。当贫血被纠正到正常对照水平时，这种改善得以实现。版权所有（c）2006 S. Karger AG，巴塞尔。
This study was intended to elucidate the efficacy of an erythropoietin analog in cardiorenal dysfunction syndrome using a rodent model. Cardiorenal dysfunction was induced using doxorubicin hydrochloride (DXR). Lower doses (3 mu g/kg) and higher doses (30 mu g/kg) of darbepoetin alfa (DA) were used for intervention. Blood examinations for creatinine, blood urea nitrogen, iron, and hemoglobin were performed until 11 weeks after starting DA administration. Urine collection was performed 10 weeks after starting DA, and protein, iron, and N-acetyl-beta-D-glucosaminidase levels and antioxidation capacity of DA were determined. The dry left ventricular heart weight was measured, when the animals were sacrificed 11 weeks after starting DA administration. Histological analyses were performed for interstitial fibrotic changes and iron deposition in the kidney. Administration of DA markedly improved anemia to the normal control level and significantly alleviated DXR-induced increases of creatinine, blood urea nitrogen, renal interstitial fibrosis, renal iron deposition, and dry left ventricular weight, but serum and urinary iron and urinary protein and N-acetyl-beta-D-glucosaminidase levels were unchanged. The urinary total radical-trapping antioxidant capacity was improved to the normal control level in DA-treated animals. DA reduced the DXR-induced cardiorenal injury. This improvement was achieved, when anemia was corrected to the normal control level. Copyright (c) 2006 S. Karger AG, Basel.