Increased gene expression of antioxidant enzymes in KKAy diabetic mice but not in STZ diabetic mice
Increased gene expression of antioxidant enzymes in KKAy diabetic mice but not in STZ diabetic mice
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DOI：
10.1016/j.diabres.2004.11.016
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发表时间：
2005-08-01
影响因子：
5.1
通讯作者：
Nanjo, K
中科院分区：
文献类型：
--
作者：
Fujita, A;Sasaki, H;Nanjo, K
在两种糖尿病小鼠模型中研究了氧化应激和抗氧化酶在转录水平上的基因表达。我们使用KKAy小鼠作为肥胖胰岛素抵抗型糖尿病的模型，并使用链脲佐菌素诱导的糖尿病小鼠（STZ小鼠）作为胰岛素缺乏型糖尿病的模型。将C57 BL小鼠和注射盐水的ICR小鼠用作相应的非糖尿病对照。为了评估氧化损伤，测定血浆丙二醛（MDA）、尿8-异前列腺素和8-羟基脱氧鸟苷（8-OHdG）。采用实时荧光定量聚合酶链反应（PCR）检测肾脏和心脏中抗氧化酶超氧化物歧化酶1（SOD-1）和谷胱甘肽过氧化物酶1（GPx-1）的mRNA表达。KKAy小鼠表现出中度高血糖和高血脂，STZ小鼠表现出重度高血糖和低血脂。相对于非糖尿病对照组，KKAy小鼠而非STZ小鼠显示出升高的血浆MDA。尿8-异前列腺素和8-OHdG在两个糖尿病小鼠组中显著增加。重度高血糖STZ小鼠尿氧化应激指标高于中度高血糖KKAy小鼠。尽管GPx-1和SOD-1在KKAy小鼠的肾脏和心脏中的mRNA表达升高，但在STZ小鼠中，与对照组相比，它们并没有增加。在胰岛素缺乏的严重高血糖状态下，抗氧化酶mRNA表达的代偿性上调可能受损。(c)2004爱思唯尔爱尔兰有限公司保留所有权利。
Oxidative stress and the gene expression at the transcriptional level of antioxidant enzymes were investigated in two models of diabetes in mice. We used KKAy mice as a model of obese insulin-resistant diabetes, and streptozotocin-induced diabetic mice (STZ mice) as a model of insulin-deficient diabetes. C57BL mice and saline-injected ICR mice were used as the respective non-diabetic controls. To assess oxidative damage, plasma malonedialdehyde (MDA), urine 8-isoprostane and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The mRNA expression of antioxidant enzymes, superoxide dismutase 1 (SOD-1) and glutathione peroxidase 1 (GPx-1) in the kidney and heart were quantified using a real-time polymerase chain reaction.The KKAy mice demonstrated moderate hyperglycemia and hyperlipidemia, and the STZ mice showed severe hyperglycemia and hypolipidemia. The KKAy mice, but not the STZ mice, showed elevated plasma MDA relative to the non-diabetic controls. Urine 8-isoprostane and 8-OHdG in both diabetic mouse groups increased significantly. The urine oxidative stress markers in the severely hyperglycemic STZ mice were higher than those in the moderately hyperglycemic KKAy mice. Although GPx-1 and SOD-1 showed elevated mRNA expression in the KKAy mice in the kidney and heart, in the STZ mice they did not increase compared to the controls. The compensatory up-regulation of the mRNA expression of antioxidant enzymes may be impaired in the insulin-deficient severely hyperglycemic state. (c) 2004 Elsevier Ireland Ltd. All rights reserved.