电针耳穴通过SIRT1/PGC-1α途径延缓D-半乳糖致衰老豚鼠听皮层老化

Effect of Electroacupuncture at Tinggong and Yifeng on D-galactose-induced Aging of Auditory Cortex through SIRT1/PGC-1α Pathway in Guinea Pigs

帅常娟;刘淑云;姚宇;杨烨;殷泽登;

1:西南医科大学附属医院耳鼻咽喉头颈外科

2:西南医科大学基础医学院生物化学教研室

摘要
目的探讨沉默信息调节因子1(silent information regulator1,SIRT1)/过氧化物酶体增殖物激活受体γ辅激活因子1α(peroxisome proliferators-activated receptor-γcoactivator 1α,PGC-1α)途径在D-半乳糖致衰老豚鼠听皮层老化中的作用以及电针耳穴是否通过该途径延缓豚鼠听皮层老化。方法 30只4月龄豚鼠随机分为对照组、D-半乳糖模型组(简称模型组)、D-半乳糖模型+电针组(简称电针组),每组10只;以10只18月龄豚鼠为老年组。模型组和电针组豚鼠颈背部皮下注射D-半乳糖(300mg·kg(-1)·d(-1)·d(-1))6周制作年龄相关性聋模型,电针组同时予以电针"听宫"穴和"翳风"穴,每日1次,每次15min,共6周;然后检测各组豚鼠ABR反应阈值,应用实时荧光定量和Westen Blot法检测各组豚鼠听皮层SIRT1和PGC-1α的mRNA和蛋白表达情况。结果模型组ABR反应阈值比对照组升高(P<0.001),电针组ABR反应阈值比模型组降低(P<0.001);模型组与老年组相比,差异无统计学意义(P>0.05)。与对照组比较,老年组和模型组SIRT1、PGC-1αmRNA和蛋白表达均降低(P<0.05);与模型组相比,电针组SIRT1、PGC-1αmRNA和蛋白表达均增加(P<0.05)。结论 SIRT1/PGC-1α信号通路参与D-半乳糖致衰老豚鼠听皮层老化过程;电针"听宫"穴和"翳风"穴可能通过激活SIRT1/PGC-1α途径,增强其听皮层抗氧化能力,从而延缓听觉中枢的老化过程。
关键词
电针;D-半乳糖;沉默信息调节因子1;过氧化物酶体增殖物激活受体γ辅激活因子1α
基金项目(Foundation):
四川省卫生厅课题(100237);; 泸州市科技局(2012-S-37);; 西南医科大学课题(20130413)资助
作者
帅常娟;刘淑云;姚宇;杨烨;殷泽登;
参考文献

1 Mikhed Y,Daiber A,Steven S,et al.Mitochondrial oxidative stress mitochondrial DNA damage and their role in agerelated vascular dysfunction[J].Int J MolSci,2015,16:15918.

2 Venkataraman K,Khurana S,Tai TC,et al.Oxidative stress in aging-matters of the heart and mind[J].Int J MolSci,2013,14:17897.

3 Sánchez-Rodríguez C,Martín-Sanz E,Cuadrado E,et al.Protective effect of polyphenols on presbycusis via oxidative/nitrosative stress suppression in rats[J].Exp Gerontol,2016,83:31.

4 Cheng Y,Takeuchi H,Sonobe Y,et al.Sirtuin 1attenuates oxidative stress via upregulation of superoxide dismutase 2and catalase in astrocytes[J].Neuroimmunol,2014,269:38.

5 Lee YH,Chen HY,Su LJ,et al.Sirtuin 1(SIRT1)deacetylase activity and NAD+/NADH ratio are imperative for capsaicin-mediated programmed cell death[J].Agric Food Chem,2015,63:7361.

6 Liu H,Sheng M,Liu Y,et al.Expression of SIRT1and oxidative stress in diabetic dry eye[J].Int J Clin Exp Pathol,2015,8:7644.

7 Tan M,Tang C,Zhang Y,et al.SIRT1/PGC-1αsignaling protects hepa-tocytes against mitochondrial oxidative stress induced by bile acids[J].Free Radic Res,2015,49:935.

8 Basu S.A complex interplay between PGC-1co-activators and mTORC1regulates hematopoietic recovery following 5-fluorouracil treatment[J].Stem Cell Res,2014,12:178.

9 李君梅,殷泽登,谢仕津,等.电针耳穴对年龄相关性聋豚鼠耳蜗核、下丘和听皮层超氧化物歧化酶活性的影响[J].中国老年学杂志,2013,33:5608.

10 Li FH,Yu HT,Xiao L,et al.Response of BAX,Bcl-2Proteins,and SIRT1/PGC-1αmRNA expression to 8-week treadmill running in the aging rat skeletal muscle[J].AdvExp Med Biol,2016,923:283.

11 Kou X,Li J,Liu X,et al.Ampelopsin attenuates the atrophy of skeletal muscle from D-gal-induced aging rats through activating AMPK/SIRT1/PGC-1αsignaling cascade[J].Biomed Pharmacother,2017,90:311.

12 Tian G,Sawashita J,Kubo H,et al.Ubiquinol-10supplementation activates mitochondria functions to decelerate senescence insenescence-accelerated mice[J].Antioxid Redox Signal,2014,20:2606.

13 赵铭辉,李胜,谯凤英,等.国内针灸治疗突发性聋临床随机对照试验文献分析[J].中国中西医结合耳鼻咽喉科杂志,2010,18:244.

14 Albuquerque AA,Rossato M,Oliveira JA,et al.Understanding the anatomy of ears from guinea pigs and rats and its use in basic otologic research[J].Braz J Otorhinolaryngol,2009,75:43.

15 谢仕津,殷泽登,李君梅,等.电针耳穴对D-半乳糖致豚鼠年龄相关性聋听觉中枢丙二醛表达的影响[J].听力学及言语疾病杂志,2012,20:254.

16 Kong WJ,Yin ZD,Fan GR,et al.Time course of neuronal and synaptic plasticity in dorsal cochlear nucleus of guinea pig following chronic kanamycin-induced deafness[J].Brain Res,2010,1328:118.

17 Schofield BR,Coomes DL.Auditory cortical projections to the cochlear nucleus in guinea pigs[J].Hear Res,2005,199:89.

18 Khan-Malek R,Wang Y.Statistical analysis of quantitative RT-PCR results[J].Methods Mol Biol,2017,1641:281.

19 秦红兵,杨朝晔,范忆江,等.D-半乳糖诱导衰老小鼠模型的建立与评价[J].中国组织工程研究与临床康复,2009,13:1275.

20 刘淑云,邓力强,杨烨,等.电针耳穴对年龄相关性听力损失豚鼠听觉中枢β-catenin表达的影响[J].听力学及言语疾病杂志,2016,24:593.

21 Wang SJ,Zhao XH,Chen W,et al.Sirtuin 1activation enhances the PGC-1α/mitochondrial antioxidant system pathway in status epilepticus[J].Mol Med Rep,2015,11:521.

22 Bu XS,Wu D,Lu XM,et al.Role of SIRT1/PGC-1αin mitochondrial oxidative stress in autistic spectrum disorder[J].Neuropsychiatr Dis Treat,2017,13:1633.

23 Di Emidio G,Falone,Vitti M,et al.SIRT1signalling protects mouse oocytes against oxidative stress and is deregulated during aging[J].Hum Reprod,2014,29:2006.

24 Xue T,Wei L,Zha DJ,et al.miR-29boverexpression induces cochlear hair cell apoptosis through the regulation of SIRT1/PGC-1αsignaling:implications for age-related hearing loss[J].Int J Mol Med,2016,38:1387.

25 Frisina RD,Ding B,Zhu X,et al.Age-related hearing loss:prevention of threshold declines,cell loss andapoptosis in spiral ganglion neurons[J].Aging(Albany NY),2016,8:2081.

26 康颂建,史献君,史永芝,等.电针对庆大霉素耳中毒的防治作用及其机制的研究[J].中国应用生理学杂志,2001,17:285.

27 张晓哲.电针针刺治疗耳鸣临床疗效对比研究[J].中国针灸,2002,22:91.

28 涂厚义,陈茜,刘淑云,等.电针听宫和翳风穴对豚鼠听皮层糖代谢及IGF-1表达的影响[J].听力学及言语疾病杂志,2015,23:280.

29 Dong W,Quo W,Wang F,et al.Electroacupuncture upregulates SIRT1-dependent PGC-1αexpression in SAMP8mice[J].Med Sci Monit,2015,21:3356.

30 Jung YS,Lee SW,Park JH,et al.Electroacupuncture preconditioning reduces ROS generation with NOX4down-regulation and ameliorates blood-brain barrier disruption after ischemic stroke[J].J Biomed Sci,2016,23:32.