氧化/抗氧化失衡在大鼠中枢听觉系统老化过程中的作用

The Role of Oxidation/Antioxidant Imbalance in the Age-related Damage of the Rat Central Auditory System

目的研究氧化/抗氧化失衡在D-半乳糖诱导的大鼠老化中枢听觉系统听皮层组织中的作用,探讨老年性耳聋氧化性损伤的发生机制。方法 48只1月龄雄性Spragua-Dawley大鼠随机分成4组(各12只),不同剂量D-半乳糖每日颈背部皮下注射D-半乳糖(500 mg/kg)造模,连续8周。造模完成后,取4组大鼠中枢听觉系统听皮层组织,检测活性氧指标过氧化氢、总抗氧化能力指标抗氧化大分子、抗氧化小分子和酶的总水平、DNA氧化损伤生物标记物8-羟基-2-脱氧鸟苷(8-OHd G)的表达以及最常发生的年龄相关性mt DNA损伤线粒体DNA(mt DNA)4 834 bp大片段缺失的累积水平。将实验数据采用方差分析进行分析。结果与对照组大鼠相比较,D-半乳糖诱导的老化大鼠听皮层组织中过氧化氢含量明显增多,而总抗氧化能力明显下降(P<0.01)。同时,DNA氧化损伤的产物8-OHd G的表达和线粒体4 834 bp大片段缺失突变的累积明显增多(P<0.01)。结论在中枢听觉系统老化过程中,氧化/抗氧化失衡可能是导致老年性耳聋发生的重要原因。

Objective To explore the effects of oxidation/antioxidant imbalance on the auditory cortex of central auditory system of D-galactose-induced aging rats and investigate the mechanism of oxidative damage of age-related hearing loss.Methods Forty-eight 1-month male Sprague-Dawley rats were randomly divided into four groups（ 12 rats in each group）,and were injected subcutaneously with different dose of D-gal once a day for 8 weeks. After the experiment termination,the tissues were harvested from the auditory cortex of central auditory system. Investigate the expression of hydrogen peroxide,total antioxidant capacity,8-hydroxy-2-deoxyguanosine（ 8-OHd G） and the accumulation of mitochondrial DNA 4 834 bp deletion.All experimental data was analysed with one-way ANOVA. Results The expression of hydrogen peroxide in the auditory cortex of rats of D-galactose groups was significantly increased compared with the control group,while the expression of the total antioxidant capacity was significantly decreased（ all P 0. 01）. Meanwhile,the expression of 8-OHd G and the accumulation of mitochondrial DNA 4 834 bp deletion were significantly increased（ P 0. 01）. Conclusions In the aging process of central auditory system,the oxidation/antioxidant imbalance may be an important cause for the age-related hearing loss.