Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice
Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice
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DOI：
10.1111/j.1365-2443.2008.01234.x
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发表时间：
2008-11-01
期刊：
影响因子：
2.1
通讯作者：
Yamamoto, Masayuki
中科院分区：
文献类型：
--
作者：
Yoh, Keigyou;Hirayama, Aki;Yamamoto, Masayuki
转录因子Nrf 2调节抗氧化基因的表达。高血糖诱导的氧化应激参与了糖尿病及其并发症的发病机制。然而，关于Nrf 2在糖尿病中的保护作用知之甚少。为了深入了解Nrf 2在糖尿病中的保护作用，我们用链脲佐菌素（STZ）处理Nrf 2敲除（Nrf 2 KO）小鼠。STZ Nrf 2 KO小鼠未发生STZ处理的野生型（STZ WT）小鼠中观察到的肾超滤，但肾功能在10周观察期内逐渐恶化。在治疗后的早期阶段，STZ Nrf 2 KO小鼠的一氧化氮代谢产物的尿排泄和肾小球病变中检测到的8-硝基鸟苷的发生增加。体内电子顺磁共振分析揭示了STZ Nrf 2 KO小鼠中3-氨基甲酰基-2，2，5，5-四甲基吡咯烷-1-氧基自旋探针信号的加速衰减速率。添加超氧化物歧化酶延长了信号的半衰期，这表明STZ Nrf 2 KO小鼠中发生了氧自由基形成增加。这些结果表明，高血糖增加氧化和亚硝化应激和加速肾损伤的Nrf 2基因敲除小鼠和Nrf 2作为防御因子对一些糖尿病并发症。
The transcription factor Nrf2 regulates the expression of antioxidant genes. Hyperglycemia-induced oxidative stress is involved in the pathogenesis of diabetes and its complications. However, little is known about the protective role of Nrf2 in diabetes. To gain insight into the protective role of Nrf2 in diabetes we treated Nrf2 knockout (Nrf2 KO) mice with streptozotocin (STZ). The STZ Nrf2 KO mice did not develop renal hyperfiltration, which was observed in the STZ-treated wild-type (STZ WT) mice, but renal function gradually deteriorated over the 10-week observation period. Urinary excretion of nitric oxide metabolites and the occurrence of 8-nitroguanosine, which was detected in glomerular lesions, were increased in STZ Nrf2 KO mice during the early stages after treatment. In vivo electron paramagnetic resonance analysis revealed an accelerated rate of decay of the 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl spin probe signal in STZ Nrf2 KO mice. The addition of superoxide dismutase prolonged the half-life of the signal, which suggested that increased oxygen radical formation occurred in the STZ Nrf2 KO mice. These results suggested that hyperglycemia increased oxidative and nitrosative stress and accelerated renal injury in the Nrf2 KO mice and that Nrf2 serves as a defense factor against some diabetic complications.