A long-term high-fat diet increases oxidative stress, mitochondrial damage and apoptosis in the inner ear of D-galactose-induced aging rats
A long-term high-fat diet increases oxidative stress, mitochondrial damage and apoptosis in the inner ear of D-galactose-induced aging rats
复制标题
长期高脂肪饮食会增加 d-半乳糖诱导的衰老大鼠内耳的氧化应激、线粒体损伤和细胞凋亡
DOI：
10.1016/j.heares.2012.04.012
复制
发表时间：
2012-05-01
期刊：
影响因子：
2.8
通讯作者：
Kong, Weijia
中科院分区：
文献类型：
--
作者：
Du, Zhengde;Yang, Yang;Kong, Weijia
在人类中，与甘油三酯升高相关的慢性血脂异常可能会降低听觉功能。然而，文献中关于长期高脂饮食（HFD）对动物内耳影响的证据很少。本研究的目的是研究12个月的HFD对Sprague-Dawley大鼠内耳和E.半乳糖（D-gal）诱导的内耳衰老过程。我们发现，12个月的HFD显着提高听觉脑干反应（ABR）的阈值在高频区。HFD可显著增加细胞内活性氧（ROS）的产生，促进NADPH氧化酶（NOX）和解偶联蛋白（UCP）的表达。此外，内耳线粒体DNA（mtDNA）共同缺失（CD）和线粒体超微结构变化的累积增加表明，存在响应于过量脂肪摄入的线粒体损伤。裂解caspase-3的表达水平和末端脱氧核苷酸转移酶（TdT）介导的脱氧尿苷三磷酸（dUTP）缺口末端标记（TUNEL）阳性细胞在内耳的数量增加的HFD。D-半乳糖对内耳的影响与12个月HFD相似。我们发现，大鼠接受HFD和D-gal表现出更大的变化，在ABR阈值，更大的增加，在表达水平的NOX，UCP和裂解的caspase-3和TUNEL阳性细胞在内耳的数量增加。目前的研究表明，HFD可能会诱导氧化应激，线粒体损伤和细胞凋亡的内耳，它提供了有关HFD和年龄相关的听力损失的风险增加之间的联系的证据。(C)2012爱思唯尔有限公司版权所有。
In humans, chronic dyslipidemia associated with elevated triglycerides may reduce auditory function. However, there is little evidence available in the literature concerning the effects of a long-term high-fat diet (HFD) on the inner ears of animals. The purpose of this study was to investigate the effect of 12 month-HFD on the inner ear of Sprague-Dawley rats and on the E.-galactose (D-gal)-induced aging process in the inner ear. We found that 12 month-HFD markedly elevated the auditory brainstem response (ABR) threshold in the high-frequency region. The HFD significantly increased the generation of reactive oxygen species (ROS) and the expressions of NADPH oxidase (NOX) and the uncoupling proteins (UCP). Furthermore, an elevated accumulation of the mitochondrial DNA (mtDNA) common deletion (CD) and mitochondrial ultrastructural changes in the inner ear suggested that there was mitochondrial damage in response to the excessive fat intake. The expression level of cleaved caspase-3 and the number of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labelling (TUNEL)-positive cells in the inner ear were increased by the HFD. The effects of D-gal on the inner ears were similar with 12 month-HFD. We found that rats receiving both the HFD and D-gal exhibited a greater shift in the ABR threshold, larger increases in the expression levels of NOX, UCP and cleaved caspase-3 and an increased number of TUNEL-positive cells in the inner ear. The present study demonstrated that HFD may induce oxidative stress, mitochondrial damage and apoptosis in the inner ear, and it provided evidence regarding the link between HFD and an increased risk of age-related hearing loss. (C) 2012 Elsevier B.V. All rights reserved.