臺灣博碩士論文加值系統

老年性失聰可能是因氧化壓力造成耳蝸神經細胞的凋亡所致，天貝被證實可經由抗氧化作用降低活性氧物質對生物體的傷害。因此本研究目的為探討天貝對老化促進小鼠(senescence accelerated prone mice；SAMP8)老年性失聰之細胞存活相關路徑之影響。實驗選用九月齡的老化促進小鼠(SAMP8)，分成未給予天貝(對照組)以及餵食900mg/Kg BW/day天貝(實驗組)，另設一組SAMR1小鼠作為SAMP8小鼠之對照(正對照組)。實驗為期12週，記錄體重、攝食量，於實驗前後進行聽性腦幹反應(auditory brainstem response, ABR)試驗，之後將動物犧牲，取其腦部腦幹及顳葉檢測超氧歧化酶(SOD)、血紅素氧化酶(Heme oxygenase-1, HO-1)、腫瘤壞死因子α(TNF-α)、介白質激素-6(IL-6)、腦衍生神經滋養因子(Brain derived neurotrophic factor, BDNF)、神經滋養受體(TrkB)的基因表現，並觀察耳蝸TNF-α及NF-κB表現量。結果顯示，在聽性腦幹反應ABR方面，天貝能有效延緩SAMP8聽力閾值的上升，抑制聽力的退化，並可顯著縮短8k耳蝸神經核到下丘及聽神經到下丘的間隔時間。在基因表現方面，老化會造成抗氧化酵素及神經保護因子之mRNA表現量下降，而發炎酵素指標之mRNA表現量上升。給予天貝後可以有效增加顳葉之HO-1、BDNF之mRNA表現量，降低TNF-α之mRNA表現量；有效減少腦幹之SOD、HO-1、BDNF之mRNA表現量；但對於顳葉及腦幹之IL-6、TrkB之表現量則無影響。在耳蝸方面，TNF-α、NF-κB表現量，在給予天貝之後在柯蒂氏器是有顯著降低。綜合上述，天貝可以改善大腦內抗氧化和發炎因子，進而提高神經傳輸能力，進而具有延緩老年性失聰之功效。

Presbycusis may be due to oxidative stress caused by the cochlear nerve cell apoptosis, and Tempeh was confirmed via antioxidant effects reduce the reactive oxygen species for damage to organisms. Thus, the purposes of this study were to examine the effect of Tempeh on cell survival pathway of presbyacusis in senescence accelerated mice. Experimental selection 9-month-old SAMP8 mice, were divided into not feeding with Tempeh(control group), as well as feeding with 900 mg/Kg BW/day tempeh(experimental groups), addition of another group of SAMR1 mice as SAMP8 mice control (positive control group). Experimental period of 12 weeks, during the recording of body weight, food intake, and the auditory brainstem response (ABR) threshold shifts on the baseline (9 months) and 12 months were analyzed, and then sacrificed the anamial, and the superoxide dismutase(SOD), heme oxygenase (Heme oxygenase-1, HO-1), tumor necrosis factor-α(TNF-α)、interleukin-6(IL-6), Brain-derived neurotrophic factor(BDNF), tyrosine kinase receptor (TrkB) mRNA expressions of brain stem, temporal lobe were also examined, and the percentage of TNF-α and NF-κB in cochlea were caculated. The results showed that the Tempeh could improve the ABR threshold and degradation of the suppression hearing in the SAMP8 mice, and reduce the interval of cochlear nucleus to inferior collicular and cochlear nerve to inferior collicular at middle frequency. In terms of gene expression, antioxidant enzymes and neuroprotection factors of mRNA expression decreased accompany with the aging progression, and indicators of inflammation enzyme of the mRNA expression increased. The supplements of tempeh significantly increase HO-1、BDNF mRNA expression, decress TNF-α mRNA expression all in temporal lobe; effectively reduce the brainstem of SOD、HO-1 and BDNF mRNA expression. However, there were not significant differences on the IL-6, TrkB mRNA expression in the temporal lobe, and brain stem among three group. In the cochlea, TNF-α、NF-κB expression after giving tempeh is significantly reduced in the organ of Corti. In summary, we conclude that tempeh could improve the antioxidant and inflammation factor in the brain, and enhanced the capacity of neuron transmission, thus delay the effect of presbycusis.

中文摘要 Ⅰ
英文摘要 Ⅱ
誌謝 Ⅳ
目錄 Ⅴ
圖目錄 Ⅷ
表目錄 Ⅹ
縮寫表 XI
第一章 前言 1
第二章 文獻回顧 3
第一節 老年性失聰 3
第二節 老化與聽力失聰之相關性 5
壹、聽覺傳導路徑 5
貳、內耳解剖生理 7
參、聽力相關檢查 10
第三節 與老年性失聰有關的相關機制 13
壹、老化與氧化壓力 13
貳、老化與發炎 15
第四節 抗氧化系統 18
第五節 腦衍生神經滋養因子與老化之相關 22
第六節 天貝(Tempeh) 24
壹、天貝簡介 24
貳、天貝之成分及營養價值 25
參、天貝的使用安全性 23
肆、天貝之生理功效 26
第七節 老化促進小鼠與聽力之相關變化 29
壹、老化促進小鼠起源 29
貳、老化促進小鼠與聽力相關研究 29
參、本實驗SAM品系來源 30
第三章 材料與方法 32
第一節 實驗動物 32
第二節 飼料組成 32
壹、飼料來源 32
貳、實驗分組與劑量 32
參、劑量換算 33
第三節 實驗流程與方法 35
第四節 聽性腦幹反應(auditory brainstem response；ABR) 37
第五節 基因表現測定 39
壹、總RNA之萃取 39
貳、反轉錄聚合酶連鎖反應(Reverse-transcriptase polymerase chain
reaction；RT-PCR) 40
參、PCR產物偵測 43
第六節 病理切片 45
壹、耳蝸病理切片 45
貳、組織切片過程 45
第七節 病理切片 47
壹、藥品與儀器設備 47
貳、免疫組織染色過程 47
第八節 統計分析 50
第四章 結果與討論 51
第一節 體重及飼料攝取量 51
第二節 器官重量 53
第三節 聽性腦幹反應試驗 56
壹、聽力閾值 56
貳、間隔時間 61
第四節 老年性失聰相關機制基因表現 65
壹、抗氧化酵素之分析 65
貳、發炎相關因子 71
參、神經保戶因子及其接受器 76
肆、TNF-α化學免疫染色法 81
伍、NF-κB化學免疫染色法 84
第五章 結論 87
第六章 參考文獻 89

行政院衛生署食品衛生處「台灣地區食品營養成份資料庫」http://www.doh.gov.tw/FoodAnalysis/ingredients.htm
林慶福，1982。天貝長久以來是落後地區之主要蛋白質來源，今後將成為文明國家之健康食品。食品工業，p15-22.
吳青蓮(1999)﹕不同月齡老化促進小白鼠之各種老化變化研究。靜宜大學食品營養學系碩士論文。
黃俊豪 (2006)：老化對於噪音環境中傾聽言語時大腦活化之影響：以功能性磁振攝影研究中樞型老年性聽障。國立台灣大學醫學院臨床醫學研究所碩士論文。
林政佑、蔡朋枝 (2009)：噪音性聽力損失與抗氧化基因易感性的相關性，以及其可能的藥物治療。工業安全科技。
郭宗勝 (2008)：以動物模式評估天貝之食用安全性及對腸道菌相的影響。靜宜大學食品營養學系碩士論文。
梁碧純(2009)：天貝對老化促進小鼠老化現象及免疫機能影響之探討。靜宜大學食品營養學系碩士論文。
張念慈(2011)：藍綠藻水萃物對於耳鳴抗氧化狀態及離子通道之影響。靜宜大學食品營養學系碩士論文。
鄭欣宜(2011)：藍綠藻水萃物對老化促進小鼠老年性聽力退化影響之探討。靜宜大學食品營養學系碩士論文。
蕭雅文(1997)：聽力學導論。五南圖書出版公司。
Abraham NG, Lavrovsky Y, Schwartzman ML, Stoltz RA, Levere RD, Gerritsen ME, Shibahara S, Kappas A. Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity. Proc. Natl. Acad. Sci. 1995;6798–6802.
Ahmad S. Antioxidant mechanisms of enzymes and proteins. In "Oxidative Stress and Antioxidant Defenses in Biology" Ahamd, S. Chapman & Hall. International Thomaon Publishing Inc. New York.1995;240-72.
Aoki H, Furuya Y, Endo Y, Fujimoto K. Effect of gamma-aminobutyric acid-enriched tempeh-like fermented soybean (GABA-tempeh) on the blood pressure of spontaneously hypertensive rats. Biosci Biotechnol Biochem. 2003;67:1806-8.
Astuti M. Superoxide dismutase in tempe, an antioxidant enzyme and its implication on health and disease. Proceedings of the International Tempe Symposium. 1997; 146–56.
Attanasio G, Viccaro M, Covelli E, De seta E, Minni A, Pizzoli F, Filipo R. Cyclo-oxygenase enzyme in the perilymph of human inner ear. Acta Otolaryngol. 2011;131:242-6.
Barbosa AC, Lajolo FM, Genovese MI. Effect of free or protein-associated soy isoflavones on the antioxidant status in rats. J Sci Food Agric. 2011;91:721-31
Beavers KM, Serra MC, Beavers DP, Cooke MB, Willoughby DS. Soy and the exercise-induced inflammatory response in postmenopausal women.Appl Physiol Nutr Metab. 2010;35:261-9.
Bisping B, Hering L, Baumann U, Denter J, Keuth S, Rehm HJ. Tempe fermentation-some aspects of formation of gamma-linolenic acid, proteases and vitamins. Biotechanol Adv. 1993;11:41-93.
Bothwell M. Functional interactions of neurotrophins and receptor. Annu Rev Neurosci. 1995;18: 223-53.
Burkard RF, Sims D. The human auditory brainstem response to high click rates: aging effects. Am J Audiol. 2001;10:53-61.
Butterfield DA, Poon HF. The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer's disease. Exp Gerontol.2005;40:774-83.
Cain K, Bratton SB, Cohen GM. The APaf-1 apoptosome : a large caspase activating complex. Biochimie. 2002;84:203-214.
Camandola S, Cutler RG, Gary DS, Milhavet O, Mattson MP. Suppression of calcium release from inositol 1,4,5-trisphosphate-sensitive stores mediates the anti-apoptotic function of nuclear factor-κB. J Biol Chem 2005;280:22287–96.
Carpinelli MR, Wise AK, Burt RA. Vitamin D-deficient diet rescues hearing loss in Klotho mice. Hear Res. 2011;275:105-9.
Chan YC, Chang SC, Liu SY, Yang HL, Hseu YC, Liao JW. Beneficial effects of yam on carbon tetrachloride-induced hepatic fibrosis in rats. J Sci Food Agric. 2010;90:161-7.
Chen J, Ruan R. Identifying stable reference genes for evaluation of antioxidative enzyme gene expression in auditory cortex and cochlea of young and old Fischer 344 rats. Acta Otolaryngol. 2009;129:644-50.
Chen W, Yao Q, Liu W, Zhang B, Wang Y, Liu B. Preventive effects of pueraria on presbycusis in rats.Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2009;23:703-5.
Choi AM, Alam J. Heme oxygenase-1﹕function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am J Respir Cell Mol Biol.1996;15:9-19.
Chung WH, Boo SH, Chung MK, Lee HS, Cho YS, Hong SH. Proapoptotic effects of NF-kappaB on cisplatin-induced cell death in auditory cell line. Acta Otolaryngol. 2008 ;128:1063-70.
Coling DE, Yu KC, Somand D, Satar B, Bai U, Huang TT, Seidman MD, Epstein CJ, Mhatre AN, Lalwani AK. Effect of SOD1 overexpression on age- and noise-related hearing loss.Free Radic Biol Med. 2003;34:873-80.
Coursin DB, Cihla HP. Pulmonary effects of short term Selenium deficiency. Thorax. 1996;51:479-83.
Cruickshanks KJ, Wiley TL, Tweed TS, Klein BE, Klein R, Mares-Perlman JA, Nondahl DM. Prevalence of hearing loss in older adults in Beaver Dam, Wisconsin. The Epidemiology of Hearing Loss Study. Am J Epidemiol. 1998;148:879-86.
Dalmas E, Nout MJ, Abee T, Roubos-van den Hil PJ. Soya bean tempe extracts show antibacterial activity against Bacillus cereus cells and spores. J Appl Microbiol. 2010;109:137-45.
Denter J, Rehm HJ, Bisping B. Changes in the contents of fat-soluble vitamins and provitamins during tempe fermentation. Int J Food Microbiol. 1998;45:129-34.
Du Z, Yang Y, Hu Y, Sun Y, Zhang S, Peng W, Zhong Y, Huang X, Kong W. A long-term high-fat diet increases oxidative stress, mitochondrial damage and apoptosis in the inner ear of d-galactose-induced aging rats. Hear Res. 2012;287:15-24.
Eckhard A, Gleiser C, Arnold H, Rask-Andersen H, Kumagami H, Müller M, Hirt B, Löwenheim H. Water channel proteins in the inner ear and their link to hearing impairment and deafness.Mol Aspects Med. 2012;33:612-37.
Ernfors P, Duan ML, ElShamy WM, Canlon B. Protection of auditory neurons from aminoglycoside toxicity by neurotrophin-3.Nat Med. 1996;2:463-7.
Esaki H, Onozaki H, Osawa T. Antioxidative activity of fermented soybean products. In; Food Phytochemicals for Cancer Prevention I.( Huang MT, Osaawa T, Ho CT and Rosen RT Eds). American Chemical Society, Washington DC, USA, 1994;353-360.
Fassini PG, Noda RW, Ferreira ES, Silva MA, Neves VA, Demonte A. Soybean glycinin improves HDL-C and suppresses the effects of rosuvastatin on hypercholesterolemic rats. Lipids Health Dis. 2011;10:165.
Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408:239-47.
Forsey RJ, Thompson JM, Ernerudh J, Hurst TL, Strindhall J, Johansson B. Plasma cytokine profiles in elderly humans. Mech. Ageing Dev. 2003; 487–493.
Fraenkel R, Freeman S, Sohmer H. Susceptibility of young adult and old rats to noise-induced hearing loss. Audiol Neurootol. 2003;8:129-39.
Francis SP, Kramarenko II, Brandon CS, Lee FS, Baker TG, Cunningham LL. Celastrol inhibits aminoglycoside-induced ototoxicity via heat shock protein 32. Cell Death Dis. 2011;2:195.
Frisina DR, Frisina RD. Speech recognition in noise and presbycusis: relation to possible neural mechanism. Hear Res. 1997;106: 95-104.
Gates GA, Mills JH. Presbycusis. Lancet. 2005;366:1111-20.
George A, Buehl A, Sommer C. Wallerian degeneration after crush injury of rat sciatic nerve increases endo- and epineurial tumor necrosis actor-alpha protein. Neurosci Lett. 2004;372:215-9.
Gopinath B, Flood VM, McMahon CM, Burlutsky G, Spankovich C, Hood LJ, Mitchell P. Dietary antioxidant intake is associated with the prevalence but not incidence of age-relatedhearing loss. J Nutr Health Aging. 2011;15:896-900.
Hernández-Ledesma B, Hsieh CC, de Lumen BO. Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages. Biochem Biophys Res Commun. 2009;390:803-8.
Hesseltine CW. A Millennium of Fungi, Food and Fermentation. Mycologia. 1965;57:149-97.
Hiramatsu M, Teranishi M, Uchida Y, Nishio N, Suzuki H, Kato K, Otake H, Yoshida T, Tagaya M, Suzuki H, Sone M, Sugiura S, Ando F, Shimokata H, Nakashima T. Polymorphisms in Genes Involved in Inflammatory Pathways in Patients with Sudden Sensorineural Hearing Loss. J Neurogenet. 2012.
Hofer M, Pagliusi SR, Hohn A, Leibrock J, Barde YA. Regional distribution of brain-derived neurotrophic factor mRNA in the adult mousebrain. Embo. J. 1990;9:2459-64.
Hong BN, Kang TH. Auditory neuropathy in streptozotocin-induced diabetic mouse. Neurosci Lett. 2008;431:268-72.
Huang Q, Tang J. Age-related hearing loss or presbycusis. Eur Arch
torhinolaryngol. 2010;267:1179-91.
Haynes L, Maue AC. Effects of aging on T cell function. Curr Opin Immunol. 2009;21:414-7.
Ishii T, Miyazawa M, Hartman PS, Ishii N. Mitochondrial superoxide anion (O2-) inducible "mev-1" animal models for aging research. BMB Rep. 2011;44:298-305.
Iwai H, Lee S, Inaba M, Sugiura K, Tomoda K, Yamashita T, Ikehara S. Prevention of accelerated presbycusis by bone marrow transplantation in senescence-accelerated mice. Bone Marrow Transplant. 2001;28:323-8.
Johnson KR, Yu H, Ding D, Jiang H, Gagnon LH, Salvi RJ. Separate and combined effects of Sod1 and Cdh23 mutations on age-related hearing loss and cochlear pathology in C57BL/6J mice. Hear Res. 2010;268:85-92.
Kannan K, Jain S. K. Oxidative stress and apoptosis . Pathophysiol. 2000;7:153-163.
Karim MR, Balsam L, Rubinstein S. Permanent hearing loss with iopamidol following aortic angiography in a hemodialysis patient：a case report and review of the literature. Am J Kidney Dis. 2010;55:712-6.
Kashio A, Amano A, Kondo Y, Sakamoto T, Iwamura H, Suzuki M, Ishigami A, Yamasoba T. Effect of vitamin C depletion on age-related hearing loss in SMP30/GNL knockout mice. Biochem Biophys Res Commun. 2009;390:394-8.
Kim SB, Lee DW, Cheigh CI, Choe EA, Lee SJ, Hong YH, Choi HJ, Pyun YR. Purification and characterization of a fibrinolytic subtilisin-like protease of Bacillus subtilis TP-6 from an Indonesian fermented soybean, Tempeh. J Ind Microbiol Biotechnol. 2006;33:436-44.
Kim SM, Chung MJ, Ha TJ, Choi HN, Jang SJ, Kim SO, Chun MH, Do SI, Choo YK, Park YI. Neuroprotective effects of black soybean anthocyanins via inactivation of ASK1-JNK/p38 pathways and mobilization of cellular sialic acids. Life Sci. 2012;90:874-82.
Kiriakidis S, Hogemeier O, Starcke S, Dombrowski F, Hahne JC, Pepper M, Jha HC, Wernert N. Novel tempeh (fermented soyabean) isoflavones inhibit in vivo angiogenesis in the chicken chorioallantoic membrane assay. Br J Nutr. 2005;93:317-23.
Klocker N, Kermer P, Weishaupt JH, Labes M, Ankerhold R, Bahr M. Brain-derived neurotrophic factor-mediated neuroprotection of adult rat retinal ganglion cells in vivo does not exclusively depend on phosphatidyl-inoditol-3’-kinase/protein kinase B signaling. J Neurosci. 2000;20:6962-7.
Kobayasi SY, Okazaki N, Koseki T. Purification and characterization of an antibiotic substance produced from Rhizopus oligosporus IFO 8631. Biosci Biotechnol Biochem. 1992;56:94-8.
Ko J. Presbycusis and its management. Br J Nurs. 2010;19:160-5.
Koob C, Kranz K, Bisping B. Degradation of α-galactosides by tempe fermentation. New Biotechnology. 2009;25:S290. Lewin GR, Barde YA. Phisiology of the neurotrophins. Annu Rev Neurosci. 1996;19:289-317.
Lammersfeld CA, King J, Walker S, Vashi PG, Grutsch JF, Lis CG, Gupta D. Prevalence, sources, and predictors of soy consumption in breast cancer. Nutr J. 2009; 22:8:2.
Lang H, Schulte BA, Zhou D, Smythe N, Spicer SS, Schmiedt RA. Nuclear factor kappaB deficiency is associated with auditory nerve degeneration and increased noise-induced hearing loss. J Neurosci. 2006;26:3541-50.
Lewin GR, Barde YA. Phisiology of the neurotrophins. Annu Rev Neurosci. 1996;19:289-317.
Lin CF. Preparation of shrimp-flavored tempeh using a thermo-tolerable Rhizopus Sp. T-3 isolated from Indonesia. Proceedings from the Symposium on Oriental Fermented Foods. Republic of China, Taipai Taiwan.1980;167-79.
Lin J, Feng L, Fukudome S, Hamajima Y, Huang T, Levine S. Cochlear stem cells/progenitors and degenerative hearing disorders. Curr Med Chem. 2007;14:2937-43.
Lindholm D, Hamner S, Zirrgiebel U, Neurotrophins and cerebellar development. Perspect Dev Neurobiol. 1997;5:83-94.
Lindsten T, Ross AJ, King A, Zong WX, Rathmell JC, Shiels HA, Ulrich E, Waymire KG, Mahar P, Frauwirth K, Chen Y, Wei M, Eng VM, Adelman DM, Simon MC, Ma A, Golden JA, Evan G, Korsmeyer SJ, MacGregor GR, Thompson CB. The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell. 2000;6:1389-99.
Liu XZ, Yan D. Ageing and hearing loss. J Pathol. 2007;211: 188-97.
Mangkuwidjoyo S, Pranowo D, Nitisuwirjo S, Noor Z. Observation on hypolipidemic activity of tempe. In Hermana H, Karyadi D,eds. Proceedings of the Symposium on the Utilization of Tempe in Health and Nutrition Development, Bogor. Nutrition Research and Development Center, Department of Health of Republic of Indonesia, 1985; 114–27.
Masuda T, Kaga K. Influence of aging over 10 years on auditory and vestibular functions in three patients with auditory neuropathy. Acta Otolaryngol. 2011;131:562-8.
Matsuo M, Nakamura N, Shidoji Y, Muto Y, Esaki H, Osawa T. Antioxidative mechanism and apoptosis induction by 3 hydroxyanthranilic acid, an antioxidant in Indonesian food tempeh, in the human hepatoma derived cell line, HUH7. J Nutr Sci Vitaminol. 1997;43:249-59.
McFadden SL, Ding D, Reaume AG, Flood DG, Salvi RJ. Age-related cochlear hair cell loss is enhanced in mice lacking copper/zinc superoxide dismutase. Neurobiol Aging. 1999;20:1-8.
Meydani SN, Wu D, Santos MS, Hayek MG. Antioxidants and immune response in aged persons: overview of present evidence. Am J Clin Nutr. 1995 ;62:1462-76.
Meen E, Blakley B, Quddusi T. Brain-derived nerve growth factor in the treatment of sensorineural hearing loss. Laryngoscope. 2009;119:1590-3.
Menardo J, Tang Y, Ladrech S, Lenoir M, Casas F, Michel C, Bourien J, Ruel J, Rebillard G, Maurice T, Puel JL, Wang J. Oxidative stress, inflammation, and autophagic stress as the key mechanisms of premature age-related hearing loss in SAMP8 mouse Cochlea. Antioxid Redox Signal. 2012;16:263-74.
Meyer AS, Isaksen A. Application of enzymes as food antioxidants. Trends in Food Sci. 1996; 6: 300-4.
Mitchell C, Phillips DS, Trune DR. Variables affecting the auditory brainstem response: audiogram, age, gender and head size. Hear Res. 1989;40:75-85.
Morse D, Choi AM. Heme oxygenase-1: the “emerging moleculae” has arrived. Am J Respir Cell Mol Biol. 2002;27: 8-16.
Nakazawa T, Kayama M, Ryu M, Kunikata H, Watanabe , Yasuda , Kinugawa J, Vavvas D, Miller JW. Tumor necrosis factor-alpha mediates photoreceptor death in a rodent model of retinal detachment. Invest Ophthalmol Vis Sci. 2011;52:1384-91.
Nagy I, Monge A, Albinger-Hegyi A, Schmid S, Bodmer D. NF-kappaB is required for survival of immature auditory hair cells in vitro. J Assoc Res Otolaryngol. 2005;6:260-8.
Nordberg J, Arnér ES. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med. 2001;31:1287-312.
Oberle S, Schwartz P, Abate A, Schroder H. The antioxidant defense protein ferritin is a novel ad specific target for pentaerithrityl tetranitrate in endothelial cells. Biochem Biophys Res Commum. 1999；28-34.
Ohlemiller KK. Age-related hearing loss: the status of Schuknecht's typology. Curr Opin Otolaryngol Head Neck Surg. 2004 ;12:439-43.
Otterbein L, Bach F, Alam J, Soares M, Tao LH, Wysk M, Davis R, Flavell R, Choi A. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med. 2000;6:285-92.
Parham K, McKinnon BJ, Eibling D, Gates GA. Challenges and opportunities in presbycusis. Otolaryngol Head Neck Surg. 2011;144:491-5.
Park HY, Lee MH, Kang SU, Hwang HS, Park K, Choung YH, Kim CH. Nitric oxide mediates TNF-α-induced apoptosis in the auditory cell line. Laryngoscope. 2012 ;19.
Ramkalawan TW. Davis AC: The effects of hearing loss and age at intervention on some language metrics in young hearing impairment children. Brit J Audiol. 1992; 26:97-107.
Reyes-Bastidas M, Reyes-Fernández EZ, López-Cervantes J, Milán-Carrillo J, Loarca-Piña GF, Reyes-Moreno C. Physicochemical, Nutritional and Antioxidant Properties of Tempeh Flour from Common Bean ( Phaseolus vulgaris L.). Food Sci Technol Int. 2010;16:427-34.
Riva C, Donadieu E, Magnan J, Lavieille JP. Age-related hearing loss in CD/1 mice is associated to ROS formation and HIF target proteins up-regulation in the cochlea. Exp Gerontol. 2007;42:327-36.
Romeo G, Glorgetti M. Therapeutic effects of vitamin E in perceptual hearing loss. Acta Vitaminol Enzymol. 1985;7:139-43.
Roubos-van den Hil PJ, Dalmas E, Nout MJ, Abee T. Soy bean tempe extracts show antibacterial activity against Bacillus cereus cell and spores. J Appl Microbiol. 2010;109:137-45.
Rüttiger L, Panford-Walsh R, Schimmang T, Tan J, Zimmermann U, Rohbock K, Köpschall I, Limberger A, Müller M, Fraenzer JT, Cimerman J, Knipper M. BDNF mRNA expression and protein localization are changed in age-related hearing loss. Neurobiol Aging. 2007;28:586-601.
Ryoya Takahashi. Anti-anging studies on the Senescence Accelerated Mouse(SAM) Strains. Yakugaku Zasshi. 2010;130:11-8.
Saitoh Y, Hosokawa M, Shimada A, Watanabe Y, Yasuda N, Takeda T, Murakami Y. Age-related hearing impairment in senescence-accelerated mouse(SAM). Hear Res. 1994;75:27-37.
Saitoh Y, Hosokawa M, Shimada A, Watanabe Y, Yasuda N, Murakami Y, Takeda T. Age-related cochlear degeneration in senescence-accelerated mouse. Neurobiol Aging. 1995;16:129-36.
Seidman MD, Khan MJ, Bai U, Shirwany N, Quirk WS. Biologic activity of mitochondrial metabolites on aging and age-related hearing loss. Am J Otol. 2000;21:161-7.
Seldman MD. Effect of dietary restriction and antioxidants on presbyacusis. Laryngoscope. 2000;110:727-38.
Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell, 1986, 46: 705-16.
Shi SS, Shao SH, Yuan BP, Pan F, Li ZL. Acute stress and chronic stress change brain-derived neurotrophic factor (BDNF) and tyrosine kinase-coupled receptor (TrkB) expression in both young and aged rat hippocampus. Yonsei Med J. 2010;51:661-71.
So H, Kim H, Lee JH, Park C, Kim Y, Kim E, Kim JK, Yun KJ, Lee KM, Lee HY, Moon SK, Lim DJ, Park R. Cisplatin cytotoxicity of auditory cells requires secretions of proinflammatory cytokines via activation of ERK and NF-kappaB. J Assoc Res Otolaryngol. 2007;8:338-55.
Someya S, Prolla TA. Mitochondrial oxidative damage and apoptosis in age-related hearing loss. Mech Ageing Dev. 2010;131:480-6.
Stanley N, Joy V. Auditory Development in the Fetus and Infant. Newborn and Infant Nursing Reviews. 2008;8:187–93.
Steinkraus KH, Cullen RE, Pederson CS, Nellis LF ,Gavitt BK. Indonesion tempeh and related fermentations, in:Handbook of Indigenous Fermented Foods 1st Edn. Marcel Dekker Publishers, New York. 1983 : 1-94,
Sudarmadji S, Suparmo S, Raharjo S. Proceedings, International Tempe Symposium. Den Pasar, Bali, Indonesia: Indonesian Tempeh Foundation, Jakarta, Indonesia. 1997.
Suta D, Rybalko N, Pelánová J, Popelář J, Syka J. Age-related changes in auditory temporal processing in the rat. Exp Gerontol. 2011;46:739-46.
Snider WD, Johnson EM. Neurotrophic molecules. Ann Neural. 1989;26:489-506.
Tabuchi K, Hoshino T, Hirose Y, Hayashi K, Nishimura B, Nakayama M, Hara A. Age-related hearing loss and expression of antioxidant enzymes in BDF1 mice. Acta Otolaryngol. 2011;131:1020-4 .
Tadros SF, D'Souza M, Zhu X, Frisina RD. Apoptosis-related genes change their expression with age and hearing loss in the mouse cochlea. Apoptosis. 2008;13:1303-21.
Takeda T. Senescence-accelerated mouse (SAM): with special reference to age-associated pathologies and their modulation. Nippon Eiseigaku Zasshi. 1996;51:569-78.
Teranishi M, Uchida Y, Nishio N, Kato K, Otake H, Yoshida T, Suzuki H, Sone M, Sugiura S, Ando F, Shimokata H, Nakashima T. Polymorphisms in Genes Involved in Oxidative Stress Response in Patients with Sudden SensorineuralHearing Loss and Ménière's Disease in a Japanese Population. DNA Cell Biol. 2012;31:1555-62.
Tha KK, Okuma Y, MiyazakiH, Murayama T, Uehara T, Hatakeyama R, Hayashi Y, Nomura Y, Changes in expressions of proinflammatory cytokines IL-1beta, TNF-alpha and IL-6 in the brain of senescence accelerated mouse (SAM)P8. Brain Res. 2000;885: 25–31.
Tilstra JS, Robinson AR, Wang J, Gregg SQ, Clauson CL, Reay DP, Nasto LA, St Croix CM, Usas A, Vo N, Huard J, Clemens PR, Stolz DB, Guttridge DC,Watkins SC, Garinis GA, Wang Y, Niedernhofer LJ, Robbins PD. NF-κB inhibition delays DNA damage-induced senescence and aging in mice. J Clin Invest. 2012;122:2601-12.
Tima Le, Elizabeth M. Keithley, Effects of antioxidants on the aging inner ear. Hear Res. 2007;226:194-202.
Tomobe K, Shinozuka T, Kuroiwa M, Nomura Y. Age-related changes of Nrf2 and phosphorylated GSK-3β in a mouse model of accelerated aging (SAMP8). Arch Gerontol Geriatr. 2012;54:1-7.
Verschuur CA, Dowell A, Syddall HE, Ntani G, Simmonds SJ, Baylis D, Gale CR, Walsh B, Cooper C, Lord JM, Sayer AA. Markers of inflammatory status are associated with hearing threshold in older people: findings from the Hertfordshire Ageing Study. Age Ageing. 2012;41:92-7.
Wang H, Brozoski TJ, Ling L, Hughes LF, Caspary DM. Impact of sound exposure and aging on brain-derived neurotrophic factor and tyrosine kinase B receptors levels in dorsal cochlear nucleus 80 days following sound exposure. Neuroscience. 2011;172:453-9.
Wang Y, Chu HQ, Zhou LQ, Chen J, Li ZY, Liu Y, Zhang P, Huang XW, Cui YH. Expression of PDCD5 and caspase 3 in the cochlea of different age of C57BL/6J mice. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2011;46:747-51.
Wei X, Zhang Y, Zhou J. Alzheimer's disease-related gene expression in the brain of senescence accelerated mouse. Neurosci Lett. 1999 ;268:139-42.
Wei YH. Mitochondrial DNA mutations and oxidative damage in aging and diseases: an emerging paradigm of gerontology and medicine. Proc Natl Sci Counc Repub China B. 1998;22:55-67.
Yamakoshi J, Fukuda S, Satoh T, Tsuji R, Saito M, Obata A. Matsuyama A, Kikuchi M, Kawasaki T. Antihypertensive and natriuretic effects of less-sodium soy sauce containing gamma-aminobutyric acid in spontaneously hypertensive rats. Biosci Biotechnol Biochem. 2007;71:165-73.
Yamamoto H, Omelchenko I, Shi X, Nuttall AL. The influence of NF-kappa B signal-transduction pathways on the murine inner ear by acoustic overstimulation. J Neurosci Res. 2009;87:1832-40.
Yamasoba T, Someya S, Yamada C, Weindruch R, Prolla TA, Tanokura M. Role of mitochondrial dysfunction and mitochondrial DNA mutations in agerelated hearing loss. Hear Res. 2007;226: 185-93.
Yan L, Graef GL, Reeves PG, Johnson LK. Selenium bioavailabilityrom soy protein isolate and tofu in rats fed a torula yeast-based diet. J Agric Food Chem. 2009;57:11575-80.
Yesilkaya A, Altinayak R, Korgun DK. The antioxidant effect of free bilirubin on cumene-hydroperoxide treated human leukocytes. Gen Pharmacol. 2000;35:17-20.
Yellon RF, Leonard G, Marucha PT, Craven R, Carpenter RJ, Lehmann WB, Burleson JA, Kreutzer DL. Characterization of cytokines present in middle ear effusions. Laryngoscope. 1991;101:165-9.
Youle RJ, Strasser A. The BCL-2 protein family: Opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008;9:47-59.
Young D, Ibuki M, Nakamori T, Fan M, Mine Y. Soy-derived di- and tripeptides alleviate colon and ileum inflammation in pigs with dextran sodium sulfate-induced colitis. J Nutr. 2012 ;142:363-8.
Yuan L, Zhou X, Li D, Ma W, Yu H, Xi Y, Xiao R. Pattern recognition receptors involved in the inflammatory attenuating effects of soybean isoflavone in β-amyloid peptides 1-42 treated rats. Neurosci Lett. 2012;506:266-70.
Zhai J, Zhou W, Li J, Hayworth CR, Zhang L, Misawa H, Klein R, Scherer SS, Balice-Gordon RJ, Kalb RG. The in vivo contribution of motor neuron TrkB receptors to mutant SOD1 motor neuron disease. Hum Mol Genet. 2011;20:4116-31.
Zhang VW, Zhang ZG, McPherson B, Hu Y, Hung YS. Detection improvement for neonatal click evoked otoacoustic emissions by time-frequency filtering. Comput Biol Med. 2011; 41:675-86.
Zhong Y, Hu YJ, Chen B, Peng W, Sun Y, Yang Y, Zhao XY, Fan GR, Huang X, Kong WJ. Mitochondrial transcription factor A overexpression and base excision repair deficiency in the inner ear of rats with D-galactose-induced aging. FEBS J. 2011;278:2500-10.