Reversal of hyperglycemia and diabetic nephropathy effect of reinstitution of good in the kidney metabolic control on oxidative stress of diabetic rats
Reversal of hyperglycemia and diabetic nephropathy effect of reinstitution of good in the kidney metabolic control on oxidative stress of diabetic rats
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DOI：
10.1016/j.jdiacomp.2004.03.002
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发表时间：
2004-09-01
影响因子：
3
通讯作者：
Odenbach, S
中科院分区：
文献类型：
--
作者：
Kowluru, RA;Abbas, SN;Odenbach, S
研究表明，良好的代谢控制(GC)有助于减缓糖尿病肾病的进展，如果在GC重新建立之前延长代谢控制不良(PC)的持续时间，肾病就不容易逆转。本研究旨在探讨GC建立后大鼠肾脏抵抗逆转的生化机制。观察糖尿病大鼠肾皮质和尿液中氧化应激和一氧化氮(NO)水平的变化，探讨糖皮质激素的再调节作用及其持续时间。在诱导高血糖后即刻或6个月后给予GC(5%糖化血红蛋白，GHb)，并在诱导糖尿病13个月后处死动物。糖尿病后即刻开始GC的大鼠，尿和肾皮质的氧化应激[以过氧化脂质(LPOS)、8-羟基-2‘-脱氧鸟苷(8-OHdG)和还原型谷胱甘肽(GSH)水平衡量]和NO水平与正常对照组无明显差异，但糖尿病后延迟6个月GC再建立后，尿和肾皮质的氧化应激和NO水平持续升高。这表明，早期启动GC可以预防高血糖诱导的氧化应激和NO，但如果PC维持较长时间，则不容易逆转。了解导致这种现象的机制可能会揭示逆转糖尿病患者肾病的新方法。(C)2004 Elsevier Inc.保留所有权利。
Studies have shown that good metabolic control (GC) is beneficial in slowing the progression of nephropathy in diabetes, and if the duration of poor metabolic control (PC) is prolonged before reinstitution of GC, nephropathy is not easily reversed. This study is to identify the biochemical abnormalities that could contribute to the resistance of nephropathy to reverse after establishment of GC in rats. The effect of reinstitution of GC and its duration is evaluated on oxidative stress and nitric oxide (NO) levels in the renal cortex and urine of diabetic rats. The rats were maintained in GC (5% glycated hemoglobin, GHb) soon after or 6 months after induction of hyperglycemia, and were sacrificed 13 months after induction of diabetes. For rats in which GC was initiated soon after induction of diabetes, oxidative stress [as measured by the levels of lipid peroxides (LPOs), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and reduced glutathione (GSH)] and NO in urine and renal cortex were not different from that observed in normal control rats, but when reinstitution of GC was delayed for 6 months after induction of diabetes, oxidative stress and NO remain elevated in both urine and renal cortex. This suggests that hyperglycemia-induced oxidative stress and NO can be prevented if GC is initiated very early, but are not easily reversed if PC is maintained for longer durations. Understanding the mechanisms responsible for this phenomenon could reveal novel means to reverse nephropathy in diabetic patients. (C) 2004 Elsevier Inc. All rights reserved.