NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats
NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats
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NADPH 氧化酶 2 介导的 Zucker 糖尿病肥胖大鼠听觉皮层的损伤
DOI：
10.1155/2019/3591605
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发表时间：
2019-07-30
影响因子：
3.1
通讯作者：
Gong, Shu-Sheng
中科院分区：
文献类型：
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作者：
Du, Zheng-De;Wei, Wei;Gong, Shu-Sheng
临床数据证实，听觉障碍可能是2型糖尿病（T2DM）的继发症状。然而，听觉系统，特别是中枢听觉系统（CAS）发生病理变化的机制仍然知之甚少。在这项研究中，Zucker糖尿病脂肪（ZDF）大鼠被用作T2DM大鼠模型，观察听觉皮层超微结构的改变，并研究T2DM中CAS损伤的可能机制。发现 ZDF 大鼠的听觉脑干反应 (ABR) 在低频率 (8kHz) 和高频率 (32kHz) 下显着升高。 ZDF 大鼠听觉皮层中 NADPH 氧化酶 2 (NOX2) 及其匹配亚基 P22phox、P47phox 和 P67phox 的蛋白表达增加。 ZDF 大鼠听觉皮层神经元线粒体中 DNA 氧化损伤标志物 8-羟基-2-脱氧鸟苷 (8-OHdG) 的表达也增加。此外，在 ZDF 大鼠的听觉皮层中检测到线粒体总抗氧化能力 (T-AOC)、三磷酸腺苷 (ATP) 产生和线粒体膜电位 (MMP) 下降，表明线粒体功能障碍。透射电镜结果表明ZDF大鼠听觉皮层神经血管单元和线粒体发生超微结构损伤。此外，在 ZDF 大鼠的听觉皮层中还检测到细胞色素 c (Cyt c) 从线粒体到细胞质的易位和 caspase 3 依赖性细胞凋亡。因此，该研究表明，T2DM 可能对 CAS 造成形态学损伤，而 NOX2 相关的线粒体氧化损伤和细胞凋亡可能是造成这种损伤的部分原因。
Clinical data has confirmed that auditory impairment may be a secondary symptom of type 2 diabetes mellitus (T2DM). However, mechanisms underlying pathologic changes that occur in the auditory system, especially in the central auditory system (CAS), remain poorly understood. In this study, Zucker diabetic fatty (ZDF) rats were used as a T2DM rat model to observe ultrastructural alterations in the auditory cortex and investigate possible mechanisms underlying CAS damage in T2DM. The auditory brainstem response (ABR) of ZDF rats was found to be markedly elevated in low (8 kHz) and high (32 kHz) frequencies. Protein expression of NADPH oxidase 2 (NOX2) and its matching subunits P22phox, P47phox, and P67phox was increased in the auditory cortex of ZDF rats. Expression of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of DNA oxidative damage, was also increased in the neuronal mitochondria of the auditory cortex of ZDF rats. Additionally, decreases in the mitochondrial total antioxidant capabilities (T-AOC), adenosine triphosphate (ATP) production, and mitochondrial membrane potential (MMP) were detected in the auditory cortex of ZDF rats, suggesting mitochondrial dysfunction. Transmission electron microscopy results indicated that ultrastructural damage had occurred to neurovascular units and mitochondria in the auditory cortex of ZDF rats. Furthermore, cytochrome c (Cyt c) translocation from mitochondria to cytoplasm and caspase 3-dependent apoptosis were also detected in the auditory cortex of ZDF rats. Consequently, the study demonstrated that T2DM may cause morphological damage to the CAS and that NOX2-associated mitochondrial oxidative damage and apoptosis may be partly responsible for this insult.