Du Zhengde, Yang Qiong, Zhou Tao, Liu Lin, Li Shuo, Chen Shixiong, Gao Chunsheng
Department of Otorhinolaryngology, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, Guangdong 518052, P.R. China.
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Mol Med Rep. 2014 Dec;10(6):2861-7. doi: 10.3892/mmr.2014.2653. Epub 2014 Oct 15.
Chronic administration of D‑galactose (D‑gal) is a useful method for establishing a model of natural aging in the auditory system. Previous studies have demonstrated that NADPH oxidases (NOXs) may be an important source of reactive oxygen species (ROS) in the peripheral auditory system (PAS) and cause an increase in mitochondrial DNA (mtDNA) common deletion (CD) levels in the PAS and central auditory system (CAS) of rats with D‑gal‑induced aging. However, the source of the ROS in the CAS and the mechanisms of age‑related hearing loss (ARHL) have yet to be elucidated. In the present study, male Sprague Dawley rats were administered a daily injection of D‑gal (150, 300 and 500 mg/kg, respectively) for eight weeks. All three doses of D‑gal caused a significant increase in the expression of NOX2, 8‑hydroxy‑2‑deoxyguanosine, a biomarker of DNA oxidative damage, and uncoupling protein 2, together with a decrease in the mitochondrial total antioxidant capabilities in the auditory cortex, as compared with the control rats (injected daily with the same volume of 0.9% saline for eight weeks). The levels of the mtDNA CD were also increased in the auditory cortex of the D‑gal‑induced aging rats. These findings suggest that both NOX‑ and mitochondria‑associated ROS generation may contribute to mtDNA oxidative damage in the auditory cortex of the CAS of D‑gal‑induced aging rats. This study may provide novel insight into the development of ARHL.
长期给予D-半乳糖（D-gal）是建立听觉系统自然衰老模型的一种有用方法。先前的研究表明，NADPH氧化酶（NOXs）可能是外周听觉系统（PAS）中活性氧（ROS）的重要来源，并导致D-半乳糖诱导衰老的大鼠PAS和中枢听觉系统（CAS）中线粒体DNA（mtDNA）常见缺失（CD）水平升高。然而，CAS中ROS的来源以及年龄相关性听力损失（ARHL）的机制尚未阐明。在本研究中，雄性Sprague Dawley大鼠每天分别注射D-半乳糖（150、300和500 mg/kg），持续8周。与对照大鼠（每天注射相同体积的0.9%生理盐水，持续8周）相比，所有三种剂量的D-半乳糖均导致听觉皮层中NOX2、DNA氧化损伤生物标志物8-羟基-2'-脱氧鸟苷和解偶联蛋白2的表达显著增加，同时线粒体总抗氧化能力降低。D-半乳糖诱导衰老大鼠的听觉皮层中mtDNA CD水平也升高。这些发现表明，NOX和线粒体相关的ROS生成可能都导致了D-半乳糖诱导衰老大鼠CAS听觉皮层中的mtDNA氧化损伤。本研究可能为ARHL的发展提供新的见解。
