發(fā)布時(shí)間：2018-02-08 22:36

  本文關(guān)鍵詞： 耳鳴 側(cè)抑制 電生理 下丘 聽覺皮層　出處：《中國人民解放軍醫(yī)學(xué)院》2013年博士論文　論文類型：學(xué)位論文

【摘要】：背景 耳鳴為無相應(yīng)的外界聲源或電刺激，而主觀存在的聲音感覺。耳鳴的發(fā)生率約為3%-30%，約有l(wèi)%-3%的人群因耳鳴而影響正常生活和工作。一些能導(dǎo)致聽力損失(噪聲暴露、老齡化、藥物、外傷)的原因均可能引起神經(jīng)性耳鳴。排除一些器質(zhì)性病變而引起的耳鳴外，常見的神經(jīng)性耳鳴多為主觀性的。由于神經(jīng)性耳鳴的客觀評定方法局限，定位診斷困難，為臨床治療難題。 耳鳴的發(fā)生機(jī)制尚不清楚，一般認(rèn)為，中樞聽覺系統(tǒng)(CAS)的抑制性神經(jīng)作用減弱，引起中樞神經(jīng)電活動(dòng)改變是耳鳴形成的神經(jīng)生理基礎(chǔ)。中樞聽覺系統(tǒng)神經(jīng)電活動(dòng)改變可能是源于耳蝸損傷，引起包括聽覺皮層(AC)、下丘(IC)和耳蝸核(CN)等中樞聽覺系統(tǒng)，某些區(qū)域的抑制功能下調(diào)。耳鳴機(jī)制的研究應(yīng)建立可靠的耳鳴動(dòng)物模型,采用行為學(xué)或電生理學(xué)方法，結(jié)合耳鳴的臨床特征進(jìn)行研究。 本文利用噪聲暴露和大劑量水楊酸鈉（SS）建立動(dòng)物模型，采用電生理學(xué)方法記錄、分析和量化，對下丘和聽覺皮層的改變進(jìn)行分類和評估。 方法與結(jié)果 第一部分 用C57小鼠作為噪聲暴露模型，16導(dǎo)微電極記錄噪聲暴露前后下丘神經(jīng)的神經(jīng)電活動(dòng)反應(yīng)情況。放電活動(dòng)結(jié)果包括頻率反應(yīng)域和放電頻率-聲音強(qiáng)度函數(shù)，頻率反應(yīng)域結(jié)果表明某些下丘神經(jīng)的特征性頻率(CF)在噪聲暴露前后由高頻區(qū)域轉(zhuǎn)變到低頻區(qū)域，某些神經(jīng)的最小閾值在噪聲暴露后升高；而某些神經(jīng)的最佳頻率和最小閾值有明顯升高；某些神經(jīng)沒有發(fā)生明顯改變。放電頻率-聲音強(qiáng)度函數(shù)表明某些低頻神經(jīng)在噪聲暴露后放電頻率會(huì)增加，而高頻神經(jīng)在噪聲暴露后放電頻率會(huì)降低。比較噪聲暴露前后的Q10值，在噪聲暴露后調(diào)諧曲線的形狀變寬，所記錄的下丘神經(jīng)自發(fā)性放電活動(dòng)比暴露前減弱。 第二部分 （1）用成年Sprague Dawley（SD）大鼠作為動(dòng)物模型，16導(dǎo)微電極記錄大劑量SS注射前后聽覺皮層神經(jīng)的放電活動(dòng)變化。腹部注射大劑量SS后3小時(shí)內(nèi)聽覺皮層放電活動(dòng)遞增。 （2）用成年SD大鼠,16導(dǎo)微電極記錄,分別研究藥物GABA類似物和鉀離子通道開放劑對大劑量SS引起的聽覺皮層高放電活動(dòng)所產(chǎn)生的影響。分別測試了GABA類似物組、GABA類似物+SS組、鉀離子通道開放劑組、鉀離子通道開放劑+SS組。藥物注射5分鐘后注射水楊酸鈉，GABA類似物+SS組和鉀離子通道開放劑+SS組的放電率增加的幅度會(huì)低于水楊酸鈉注射組。這表明GABA類似物和鉀離子通道開放劑可部分抑制水楊酸鈉引起的聽覺皮層高放電活動(dòng)。 結(jié)論 （1）噪聲暴露可能引起下丘中樞側(cè)抑制的損傷，這些抑制性區(qū)域一般存在于比下丘神經(jīng)的特征性頻率（CF）較低的頻率區(qū)域，CF遷移和調(diào)諧曲線變寬主要發(fā)生在高于噪聲暴露頻率的神經(jīng)區(qū)域，噪聲暴露后下丘神經(jīng)自發(fā)性放電即刻降低，，這不同于噪聲暴露一段時(shí)間后自發(fā)性放電的改變。上述電活動(dòng)改變表明噪聲暴露后耳蝸接受到的傳入神經(jīng)信號減少，影響正常的聽覺傳導(dǎo)通路，下丘神經(jīng)的可塑性變化可能是引起耳鳴的原因，并解釋了噪聲引起的耳鳴頻率范圍與噪聲的頻率有關(guān)，即耳鳴的頻率常低于噪聲暴露頻率。 （2）大劑量水楊酸鈉可以引起聽覺皮層放電頻率增高，GABA類似物和鉀離子通道開放劑可以降低聽覺皮層的放電頻率，這兩種藥物對大劑量水楊酸鈉對聽覺皮層的電生理功能均有影響。GABA類似物和鉀離子通道開放劑可能對耳鳴有抑制作用。 上述研究會(huì)幫助我們進(jìn)一步認(rèn)識耳鳴的發(fā)生機(jī)制，對于耳鳴治療也提供了線索。
[Abstract]:background
Tinnitus without corresponding external sound source or electrical stimulation, and the sound of subjective feeling. The incidence of 3%-30% is about tinnitus, about l%-3% of the population because of tinnitus and affect the normal life and work. Some can cause hearing loss (noise exposure, aging, drugs, trauma) causes are likely to cause nerve tinnitus. Some organic lesions caused by tinnitus, nervous tinnitus is common. Due to the limitations of subjective objective evaluation methods of nervous tinnitus, positioning diagnostic difficulties for clinical treatment problems.
The mechanism of tinnitus is unclear, is generally believed that the central auditory system (CAS). The inhibitory nerve function, caused by the electrical activity of CNS neural and physiological basis of tinnitus change is formed. The electrical activity of auditory CNS changes may be due to the induced cochlear injury, including auditory cortex, inferior colliculus (IC (AC)) and cochlear nucleus (CN) and the central auditory system, inhibit the function of certain areas down. Mechanism of tinnitus research should establish a reliable animal model of tinnitus, using behavioral or electrophysiological methods, combined with the clinical characteristics of tinnitus in research.
The animal models were established by noise exposure and high-dose sodium salicylate (SS). The changes in the inferior colliculus and auditory cortex were classified and evaluated by electrophysiological methods.
Methods and results
Part one
Using C57 mice as a model of noise exposure, 16 by neural activity reaction were recorded before and after noise exposure. The inferior colliculus neuron discharge activity including frequency response area and discharge frequency - sound intensity function, frequency response characteristic frequency domain results show that some IC nerve (CF) in the high frequency region after noise exposure to low frequency area, the minimum threshold of certain nerves increased in noise exposure; and the optimum frequency of certain nerves and minimum threshold increased significantly; some nerve showed no change. The discharge frequency of sound intensity function shows that some low frequency noise exposure in nerve discharge frequency will increase, while the high frequency noise exposure in nerve discharge frequency will be reduced. Comparison of the Q10 values before and after noise exposure, the noise exposure tuning curve shape becomes wide, spontaneous discharge recorded neural activity in inferior colliculus than Abate before exposure.
The second part
(1) Adult Sprague Dawley (SD) rats were used as animal models, and 16 guided microelectrodes recorded the changes of nerve activity in auditory cortex before and after high-dose SS injection. After 3 hours of abdominal injection, the activity of auditory cortex increased.
(2) with adult SD rats, 16 channel microelectrode recording, respectively studies the influence drug GABA analogues and potassium channel openers on high dose SS induced auditory cortex produced high discharge activity. Tested the GABA analogue group, GABA analogue group +SS, potassium channel opener group. Potassium channel opener +SS group. Drug injection 5 minutes after injection of sodium salicylate, discharge GABA analogue group +SS and potassium channel opener +SS group the rate of increase is lower than sodium salicylate injection group. This indicated that GABA analogues and potassium channel openers can inhibit sodium salicylate induced auditory cortex high discharge activity.
conclusion
(1) may cause central lateral inhibition injury of inferior colliculus noise exposure, these inhibitory regions generally exist in the ratio of characteristic frequency inferior colliculus (CF) nerve in the lower frequency region, CF migration and wide tuning curve occurs mainly in the neural region is higher than the frequency of noise exposure, inferior colliculus neuron spontaneous discharge of immediate reduction in noise exposure after the noise exposure is different from the change of spontaneous discharge after a period of time. The change shows that the electrical activity of afferent signal after noise exposure to reduce the influence of the cochlea, auditory pathway normal, plasticity of hypothalamic nerve may cause tinnitus, and explain the noise induced tinnitus frequency range and noise the frequency, the frequency of tinnitus is often less than the frequency of noise exposure.
(2) a large dose of sodium salicylate can cause the auditory cortex increased the discharge frequency, discharge frequency of GABA analogues and potassium channel openers can reduce the auditory cortex, these two kinds of drugs on a large dose of sodium salicylate on the auditory cortex electrical physiological function of both.GABA analogues and potassium channel openers may have an inhibitory effect on the tinnitus.
The above research will help us to further understand the mechanism of tinnitus and provide clues for the treatment of tinnitus.

【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2013
【分類號】：R764.45

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