Zhang A R, Ma K F, She X J, Liu H T, Cui B, Wang R
Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University and shandong Acacdemy of Medical Sciences, Jinan 250062, China Institute of Environmental and Operational Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Tianjin 300050, China.
Institute of Environmental and Operational Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Tianjin 300050, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2022 Apr 20;40(4):248-254. doi: 10.3760/cma.j.cn121094-20210719-00355.
To study the protective effects of metformin on noise-induced hearing loss (NIHL) and its differential protein omics expression profile. In January 2021, 39 male Wistar rats were randomly divided into control group, noise exposure group and metformin+noise exposure group, with 13 rats in each group. Rats in the noise exposure group and metformin+noise exposure group were continuously exposed to octave noise with sound pressure level of 120 dB (A) and center frequency of 8 kHz for 4 h. Rats in the metformin+noise exposure group were treated with 200 mg/kg/d metformin 3 d before noise exposure for a total of 7 d. Auditory brainstem response (ABR) was used to test the changes of hearing thresholds before noise exposure and 1, 4, 7 d after noise exposure in the right ear of rats in each group. Tandem mass tag (TMT) quantitative proteomics was used to identify and analyze the differentially expressed protein in the inner ear of rats in each group, and it was verified by immunofluorescence staining with frozen sections. The click-ABR thresholds of right ear in the noise exposure group and metformin+noise exposure group were significantly higher than those in the control group 1, 4, 7 d after noise exposure (<0.05) . The click-ABR threshold of right ear in the metformin+noise exposure group were significantly lower than that in the noise exposure group (<0.05) . Compared with the noise exposure group, 1035 up-regulated proteins and 1145 down-regulated proteins were differentially expressed in the metformin+noise exposure group. GO enrichment analysis showed that the significantly differentially expressed proteins were mainly involved in binding, molecular function regulation, signal transduction, and other functions. Enrichment analysis of KEGG pathway revealed that the pathways for significant enrichment of differentially expressed proteins included phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway, focal adhesion, diabetic cardiomyopathy, mitogen, and mitogen-activated protein kinase (MAPK) signaling pathway. Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased. Noise exposure can lead to an increase in rat hearing threshold, and metformin can improve noise-induced hearing threshold abnormalities through multiple pathways and biological processes.
研究二甲双胍对噪声性听力损失（NIHL）的保护作用及其差异蛋白质组学表达谱。2021年1月，将39只雄性Wistar大鼠随机分为对照组、噪声暴露组和二甲双胍+噪声暴露组，每组13只。噪声暴露组和二甲双胍+噪声暴露组的大鼠连续暴露于声压级为120 dB（A）、中心频率为8 kHz的倍频程噪声4小时。二甲双胍+噪声暴露组的大鼠在噪声暴露前3天用200 mg/kg/d的二甲双胍治疗，共7天。采用听性脑干反应（ABR）检测每组大鼠噪声暴露前及暴露后1、4、7天右耳听力阈值的变化。采用串联质谱标签（TMT）定量蛋白质组学技术对每组大鼠内耳差异表达蛋白进行鉴定和分析，并用冰冻切片免疫荧光染色进行验证。噪声暴露组和二甲双胍+噪声暴露组大鼠右耳的短声ABR阈值在噪声暴露后1、4、7天均显著高于对照组（<0.05）。二甲双胍+噪声暴露组大鼠右耳的短声ABR阈值显著低于噪声暴露组（<0.05）。与噪声暴露组相比，二甲双胍+噪声暴露组有1035个上调蛋白和1145个下调蛋白差异表达。基因本体（GO）富集分析表明，显著差异表达的蛋白质主要参与结合、分子功能调控、信号转导等功能。京都基因与基因组百科全书（KEGG）通路富集分析显示，差异表达蛋白显著富集的通路包括磷脂酰肌醇3激酶-蛋白激酶B（PI3K-Akt）信号通路、粘着斑、糖尿病心肌病、丝裂原和丝裂原活化蛋白激酶（MAPK）信号通路。免疫荧光实验表明，与噪声暴露组相比，二甲双胍+噪声暴露组胰岛素样生长因子1受体（IGF1R）的荧光强度增加，真核翻译起始因子4E结合蛋白1（eIF4EBP1）的荧光强度降低。噪声暴露可导致大鼠听力阈值升高，二甲双胍可通过多种途径和生物学过程改善噪声引起的听力阈值异常。
