Fujita Atsuyo, Sasaki Hideyuki, Ogawa Kenichi, Okamoto Kunihisa, Matsuno Shohei, Matsumoto Eisaku, Furuta Hiroto, Nishi Masahiro, Nakao Taisei, Tsuno Takuo, Taniguchi Hisaji, Nanjo Kishio
The First department of Medicine, Wakayama Medical University, Kimiidera 811-1, Wakayama, P.O. 641-8509, Japan.
Diabetes Res Clin Pract. 2005 Aug;69(2):113-9. doi: 10.1016/j.diabres.2004.11.016.
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.
在两种小鼠糖尿病模型中研究了氧化应激及抗氧化酶转录水平的基因表达。我们使用KKAy小鼠作为肥胖胰岛素抵抗性糖尿病模型，链脲佐菌素诱导的糖尿病小鼠（STZ小鼠）作为胰岛素缺乏性糖尿病模型。C57BL小鼠和注射生理盐水的ICR小鼠分别用作非糖尿病对照。为评估氧化损伤，检测了血浆丙二醛（MDA）、尿8-异前列腺素和8-羟基脱氧鸟苷（8-OHdG）。使用实时聚合酶链反应定量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脂血症，STZ小鼠表现出严重高血糖和低脂血症。与非糖尿病对照相比，KKAy小鼠血浆MDA升高，而STZ小鼠未升高。两个糖尿病小鼠组的尿8-异前列腺素和8-OHdG均显著增加。严重高血糖的STZ小鼠的尿氧化应激标志物高于中度高血糖的KKAy小鼠。尽管KKAy小鼠肾脏和心脏中GPx-1和SOD-1的mRNA表达升高，但与对照相比，STZ小鼠中它们并未增加。抗氧化酶mRNA表达的代偿性上调在胰岛素缺乏的严重高血糖状态下可能受损。
