Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress.
Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress.
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DOI：
10.3892/mmr.2012.1227
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发表时间：
2013-02
影响因子：
3.4
通讯作者：
Hong-Ying Yang;Shourui Fan;D. Song;Zhuo Wang;Shungao Ma;Shuqing Li;Xiaohong Li;Mian Xu;Min Xu;Xianmo Wang
中科院分区：
文献类型：
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作者：
Hong-Ying Yang;Shourui Fan;D. Song;Zhuo Wang;Shungao Ma;Shuqing Li;Xiaohong Li;Mian Xu;Min Xu;Xianmo Wang
本研究旨在探讨链脲佐菌素（STZ）诱导的糖尿病（DM）大鼠不同阶段的病理生理学变化和氧化应激。雄性Sprague-Dawley大鼠（120只）随机分为DM组和对照组。测定大鼠体质量、血糖、糖化血红蛋白（HbA 1c）、脑组织和血清超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）及醛糖还原酶（AR）活性。电镜观察脑内神经元和血管的变化。与对照组相比，STZ治疗组大鼠的血糖、低密度脂蛋白、甘油三酯和总胆固醇水平升高1.43 - 3.0倍，高密度脂蛋白、HbA 1c和胰岛素敏感性指数升高1.1 - 1.23倍。在治疗后第16周，DM大鼠血清H2 O2浓度增加，表明氧化应激和GPx和SOD的mRNA水平比对照组高2倍。蛋白GPx和SOD水平降低（P<0.01）。糖尿病大鼠早期肾小球毛细血管基底膜不规则增厚，线粒体及上皮细胞空泡化。随着时间的推移，DM大鼠脑中的神经元细胞和血管变得越来越异常，高尔基体、线粒体和内质网的变化，同时伴有SOD失活和AR蛋白的积累。STZ诱导的DM大鼠的疾病进展包括伴有血管和神经元细胞异常的脑病理，与SOD、CAT和GPx活性降低以及AR蓄积相关。
The aim of this study was to investigate pathophysiological alterations and oxidative stress in various stages of streptozotocin (STZ)‑induced diabetes mellitus (DM) in rats. Male Sprague-Dawley rats (120) were randomized into DM and control groups. Body mass, plasma glucose, glycated hemoglobin (HbA1c), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, as well as aldose reductase (AR) activities, in brain tissue and serum were determined. Electron microscopy was used to observe neuron and vessel changes in the brain. In STZ‑treated rats, blood glucose, low density lipoproteins, triglycerides and total cholesterol levels increased 1.43‑3.0‑fold and high density lipoprotein, HbA1c and insulin sensitivity index increased 1.1‑1.23‑fold compared with control. At week 16 following treatment, DM rat serum H2O2 concentration was increased, indicating oxidative stress and mRNA levels of GPx and SOD were 2‑fold higher than the control. Protein GPx and SOD levels were reduced (P<0.01). DM rats were identified to exhibit early irregular glomerular capillary basement membrane thickening and vacuolization in the mitochondria and epithelial cells. Neuron cells and blood vessels in the DM rat brains became increasingly abnormal over time with altered Golgi bodies, mitochondria and endoplasmic reticulum cisterns, concurrent with SOD inactivation and AR protein accumulation. Disease progression in rats with STZ‑induced DM included brain pathologies with vascular and neuron cell abnormalities, associated with the reduction of SOD, CAT and GPx activities and also AR accumulation.