水杨酸钠致耳鸣大鼠脑海马区促肾上腺皮质激素释放因子的表达

The Expression of Corticotropin-Releasing Factor in Rat's Hippocampus Involves in the Pathology of Salicylate Induced Tinnitus

解为全;廖华;杨希林;陈抗松;邹哲飞;李暐;

1:武汉大学人民医院耳鼻咽喉-头颈外科

摘要
目的观察水杨酸纳致耳鸣大鼠海马区促肾上腺皮质激素释放因子(corticotropin-releasing factor,CRF)的表达,探讨其参与水杨酸钠致耳鸣的可能机制。方法将ABR反应阈<30dB SPL的30只健康Wistar大鼠随机分为A、B、C三组,每组10只。A组注射10%水杨酸钠溶液350mg.kg-1.d-1,共注射21天,B组注射10%水杨酸钠溶液350mg.kg-1.d-1,共注射14天,C组(对照组)腹腔注射等量生理盐水14天。给药前采用改良的饮水抑制法对各组大鼠进行条件反射训练,条件反射消退期开始注射水杨酸钠并检测各组大鼠饮水抑制率(R值);分别于给药前两天、首次给药后2h、给药结束后当天检测各组大鼠ABR反应阈,然后将大鼠处死并断头取脑,剥离海马区,采用Western blot方法检测CRF在各组大鼠海马区的表达。结果条件反射消退期1~3天A、B两组大鼠R值大于C组(P<0.05),证明耳鸣大鼠模型建立成功;首次给药后2h及给药结束后A、B两组ABR反应阈均较给药前提高了约30dB(P<0.05),但A、B两组间ABR反应阈差异无统计学意义(P>0.05);大鼠脑海马区CRF表达量A组>B组>C组(P<0.05)。结论水杨酸钠注射致耳鸣大鼠的海马区情绪应激相关蛋白CRF表达增强,且随注射时间延长其表达量增加,提示CRF表达升高可能是边缘系统参与耳鸣的重要机制之一。
关键词
水杨酸钠;耳鸣;促肾上腺皮质激素释放因子;海马
基金项目(Foundation):
国家自然科学基金面上项目(30772397)资助
作者
解为全;廖华;杨希林;陈抗松;邹哲飞;李暐;
参考文献

1孔维佳,耳鼻咽喉头颈外科学[M].第二版.北京:人民卫生出版社,2010.201~205.

2黎志成,古若雷,曾祥丽,耳鸣的心理机制[J].心理科学进展,2011,19:1 179.

3 Jastreboff PJ.Phantom auditory perception(tinnitus):mech-anisms of generation and perception[J].Neuroscience Re-search,1990,8:221.

4 Jastreboff PJ,Brennan JF,Coleman JK,etc.Phantom audi-tory sensation in rats:an animal model for tinnitus[J].Behav-ioral Neuroscience,1988,102:811.

5 George P,Watson C.The rat brain in stereotaxic coordinates[M].Academic Press,2007.26~45.

6 Mizuno K,Giese KP.Hippocampus-dependent memory for-mation:do memory type-specific mechanisms exist[J]?J Pharmacol Sci,2005,98:191.

7 Dautzenberg FM,Hauger RL.The CRF peptide family and their receptors:yet more partners discovered[J].Trends in Pharmacological Science,2002,23:71.

8 Wang XD,Rammes G,Kraev I,et al.Forebrain CRF1modu-lates early-life stress-programmed cognitive deficits[J].J Neurosci,2011,31:13 625.

9 Marinkovic I,Lyytinen J,Valanne L,et al.Bilateral hipp-ocampal infarction as etiology of sudden and prolonged memory loss[J].Case Rep Neurol,2012,4:207.

10 Mirz F,Gjedde A,Sdkilde-Jrgensen H,et al.Functional brain imaging of tinnitus-like perception induced by aversive auditory stimuli[J].Neuroreport,2000,11:633.

11 O'Mara S.The subiculum:what it does,what it might do,and what neuroanatomy has yet to tell us[J].J Anat,2005,207:271.

12 Munoz-Lopez MM,Mohedano-Moriano A,Insausti R.Anatomical pathways for auditory memory in primates[J].Front Neuroanat,2010,4:1.

13 Graham CE,Vetter DE.The mouse cochlea expresses a local hypothalamic-pituitary-adrenal equivalent signaling system and requires corticotropin-releasing factor receptor 1to es-tablish normal hair cell innervation and cochlear sensitivity[J].The Journal of Neuroscience,2011,31:1 267.

14 Kaltenbach JA.Tinnitus:models and mechanisms[J].Hearing Research,2011,276:52.

15 Liu XP,Chen L.Auditory brainstem response as a possible objective indicator for salicylate-induced tinnitus in rats[J].Brain Research,2012,1 485:88.

16 Yang G,Lobarinas E,Zhang L,et al.Salicylate induced tin-nitus:behavioral measures and neural activity in auditory cor-tex of awake rats[J].Hearing Research,2007,226:244.