Yang Lu, Zheng Shirong, Epstein Paul N
Department of Pharmacology and Toxicology, University of Louisville, KY, USA.
Free Radic Res. 2009 Feb;43(2):174-82. doi: 10.1080/10715760802657308.
Adriamycin (ADR) is nephrotoxic. One component of ADR-induced nephropathy may be oxidative stress. This study used a recently developed line of transgenic mice (Nmt) on the FVB background strain, which over-express the antioxidant protein metallothionein (MT) in podocytes. Cultured podocytes from Nmt mice were resistant to H(2)O(2) injury, as judged by disruption of F-actin filaments. FVB control and transgenic mice received 11 mg/kg body weight ADR by tail vein injection and 24-h urine samples were then collected for albumin analysis. Also renal morphology was investigated by light and electron microscopy. Urine albumin analysis showed that ADR treatment significantly increased albuminuria in control mice, indicating that the FVB strain is sensitive to ADR nephropathy and Nmt mice were significantly protected from elevated albuminuria. Glomerular histopathology revealed that ADR reduced podocyte number and produced foot process effacement in FVB mice. The Nmt transgene protected podocyte numbers and podocyte foot processes from the effects of ADR. These results show that metallothionein can protect podocytes from ADR toxicity.
阿霉素（ADR）具有肾毒性。ADR诱导的肾病的一个组成部分可能是氧化应激。本研究使用了最近培育出的FVB背景品系的转基因小鼠（Nmt），其足细胞中抗氧化蛋白金属硫蛋白（MT）过表达。通过F-肌动蛋白丝的破坏判断，来自Nmt小鼠的培养足细胞对H₂O₂损伤具有抗性。FVB对照小鼠和转基因小鼠通过尾静脉注射给予11 mg/kg体重的ADR，然后收集24小时尿液样本进行白蛋白分析。同时通过光镜和电镜研究肾脏形态。尿液白蛋白分析表明，ADR处理显著增加了对照小鼠的蛋白尿，表明FVB品系对ADR肾病敏感，而Nmt小鼠的蛋白尿升高得到了显著保护。肾小球组织病理学显示，ADR减少了FVB小鼠的足细胞数量并导致足突消失。Nmt转基因保护足细胞数量和足细胞足突免受ADR的影响。这些结果表明，金属硫蛋白可以保护足细胞免受ADR毒性。
