Nrf2及其信号通路相关因子在噪声性聋大鼠耳蜗的表达

Expression of Nrf2 and Its Related Factors in the Cochlea of Rats with Noise Induced Hearing Loss

目的研究Nrf2/Keapl-ARE信号通路相关因子核因子2(nuclear factor E2related factor 2,Nrf2)、超氧化物歧化酶1(superoxide dismutas 1,SOD1)、血红素加氧酶1(heme oxygenase-1,HO-1)在噪声致聋大鼠耳蜗的表达变化。方法 SD大鼠30只,随机分为噪声组15只和正常对照组15只。正常对照组不给予噪声暴露,噪声组动物给予连续12小时115dB SPL的稳态白噪声暴露,分别于噪声暴露后1、3、7天对两组动物进行ABR和DPOAE检测,并于噪声暴露7天后取耳蜗组织运用RT-PCR技术及Peggy Sue微量蛋白检测技术检测Nrf2、SOD1、HO-1的表达。结果噪声暴露后1、3、7天,噪声组大鼠ABR反应阈均高于正常对照组(P<0.05),噪声组DPOAE幅值较正常组明显下降(P<0.05);噪声暴露后7天,噪声组大鼠耳蜗Nrf2、SOD1、HO-1的mRNA表达(1.11±0.05、1.45±0.12、1.15±0.03)上调,高于正常对照组(1.00±0.02、1.10±0.12、0.92±0.08),差异均有统计学意义(P<0.05)。Peggy Sue微量检测系统检测结果显示噪声组Nrf2及SOD1、HO-1蛋白含量均高于正常组(P<0.05)。结论强噪声暴露后,SD大鼠耳蜗Nrf2基因表达和蛋白含量升高,Nrf2/Keapl-ARE信号通路下游抗氧化酶SOD1、HO-1基因表达和蛋白含量也随即上调,此改变可能对噪声引起的耳蜗内氧化应激损伤有一定的保护作用。

Objective To study the expression of Nuclear factor E2 related factor 2（Nrf2）,Superoxide Dismutas 1（SOD1）,and Heme Oxygenase- 1（HO-1）factors related to Nrf2 signaling pathway in noise-induced cochlear injury of rats.Methods A total of 30 SD rats were randomly and equally assigned into the following 2groups：noise group and normal control group.The rats in noise group were exposed to an 115 dB SPL continuous steady white noise for 12 hours,then 1day,3days,and 7days later,the rats receveid the ABR and DPOAE testing after noise exposure.Both RT-PCR and Peggy Sue trace protein detection techniques were used to detect gene expression in Nrf2/Keapl-ARE signaling pathway and the protein levels by cochlear tissue sampling after noise exposure 7days later.Results The ABR thresholds in the noise group was higher than those of in normal control group after noise exposure 1,3,and 7days later（P〈0.05）.The DPOAE values of noise group were significantly lower than those of normal control group（P〈0.05）.The up-regulation of expression of Nrf2,SOD1,HO-1mRNA（1.11±0.05,1.45±0.12,1.15±0.03）in noise group were higher than those of in the normal control group after noise exposure 7days later（1.00±0.02,1.10±0.12,0.92±0.08）,and the differences were statistically significant（P〈0.05）.And in Peggy Sue trace detection system,we also found SOD1,HO-1protein levels in noise group were higher than those of in normal control group.Conclusion After the noise-induced cochlear injury in rat,Nrf2 expression in the cochlea increased and up-regulatd expression of downstream gene and protein content such as antioxidant enzymes SOD1 and HO-1gene by regulating Nrf2/Keapl-ARE signaling pathway,which may be involved in protection against oxidative stress injury in noise-induced cochlear injury of rat.