發(fā)布時(shí)間：2018-01-27 14:18

  本文關(guān)鍵詞： 水楊酸鈉 耳鳴 海馬神經(jīng)元 電壓門(mén)控性離子通道 全細(xì)胞膜片鉗　出處：《河北醫(yī)科大學(xué)》2012年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：耳鳴是一種常見(jiàn)的聽(tīng)覺(jué)系統(tǒng)疾病，其特點(diǎn)是在無(wú)外部相應(yīng)聲源的情況下耳內(nèi)出現(xiàn)的幽靈般的鈴音或蜂鳴聲，是一種主觀的聲音感覺(jué)。臨床醫(yī)生已經(jīng)注意到了耳鳴和情緒狀態(tài)之間的關(guān)系。近年來(lái)有研究發(fā)現(xiàn)邊緣系統(tǒng)某些相關(guān)核團(tuán)參與耳鳴的不良情緒形成，例如海馬。水楊酸鈉過(guò)量能夠引起耳鳴，是研究耳鳴發(fā)生機(jī)制的重要的工具藥。本課題利用全細(xì)胞膜片鉗技術(shù)研究水楊酸鈉對(duì)大鼠海馬部位神經(jīng)元上的電壓門(mén)控性鉀、鈉、鈣離子通道的影響，探討海馬神經(jīng)元上電壓門(mén)控性離子通道與耳鳴的不良情緒之間的關(guān)系。一共分為三部分： 一、水楊酸鈉對(duì)海馬神經(jīng)元電壓門(mén)控性鉀離子通道的影響 目的和方法：本實(shí)驗(yàn)利用腦片膜片鉗技術(shù)觀察水楊酸鈉對(duì)大鼠海馬神經(jīng)元瞬時(shí)外向鉀通道和延遲整流鉀通道的影響。觀察給予1mM水楊酸鈉前后，IK(A)和IK(DR)的I-V曲線(xiàn)、穩(wěn)態(tài)激活曲線(xiàn)、穩(wěn)態(tài)失活曲線(xiàn)的變化情況。 結(jié)果：水楊酸鈉對(duì)IK(A)和IK(DR)均有抑制作用，且具有濃度依賴(lài)性。水楊酸鈉對(duì)IK(A)的穩(wěn)態(tài)激活動(dòng)力學(xué)和穩(wěn)態(tài)失活動(dòng)力學(xué)沒(méi)有影響。但是對(duì)IK(DR)的穩(wěn)態(tài)激活動(dòng)力學(xué)和穩(wěn)態(tài)失活動(dòng)力學(xué)均有影響。1mM的水楊酸鈉使IK(DR)的穩(wěn)態(tài)激活曲線(xiàn)向超極化方向移動(dòng)大約12mV，穩(wěn)態(tài)失活曲線(xiàn)向超極化方向移動(dòng)大約19mV。 結(jié)論：水楊酸鈉通過(guò)對(duì)海馬部位神經(jīng)元上的瞬時(shí)外向鉀通道和延遲整流鉀通道的抑制作用，使動(dòng)作電位的持續(xù)時(shí)間延長(zhǎng)，增強(qiáng)神經(jīng)遞質(zhì)的釋放，加快神經(jīng)元的重復(fù)放電節(jié)律，提高神經(jīng)元的興奮性。 二、水楊酸鈉對(duì)海馬神經(jīng)元電壓門(mén)控性鈉離子通道的影響 目的和方法：本實(shí)驗(yàn)我們利用腦片膜片鉗技術(shù)觀察水楊酸鈉對(duì)大鼠海馬神經(jīng)元電壓門(mén)控性鈉通道電生理學(xué)特征的影響。觀察了給予1mM水楊酸鈉前后，INA的I-V曲線(xiàn)、穩(wěn)態(tài)激活曲線(xiàn)、穩(wěn)態(tài)失活曲線(xiàn)的變化情況。 結(jié)果：水楊酸鈉對(duì)INA有抑制作用，且具有濃度依賴(lài)性。水楊酸鈉對(duì)INA的穩(wěn)態(tài)激活曲線(xiàn)有影響，使其穩(wěn)態(tài)激活曲線(xiàn)向超極化方向移動(dòng)10mV左右，但是對(duì)其的穩(wěn)態(tài)失活曲線(xiàn)沒(méi)有影響。 結(jié)論：水楊酸鈉通過(guò)對(duì)海馬部位神經(jīng)元上的電壓門(mén)控性鈉離子通道的抑制作用，降低動(dòng)作電位產(chǎn)生的閾值，提高神經(jīng)元的興奮性，，使神經(jīng)元處于過(guò)度興奮狀態(tài)，促進(jìn)神經(jīng)元的重復(fù)放電和神經(jīng)遞質(zhì)的釋放。 三、水楊酸鈉對(duì)海馬神經(jīng)元電壓門(mén)控性鈣離子通道的影響 目的和方法：本實(shí)驗(yàn)利用腦片膜片鉗技術(shù)觀察水楊酸鈉對(duì)大鼠海馬神經(jīng)元電壓門(mén)控性鈣離子通道電生理學(xué)特性的影響。觀察了給予1mM水楊酸鈉前后，ICa的I-V曲線(xiàn)、穩(wěn)態(tài)激活曲線(xiàn)、穩(wěn)態(tài)失活曲線(xiàn)的變化情況。 結(jié)果:水楊酸鈉對(duì)ICa有抑制作用而且具有濃度依賴(lài)性。水楊酸鈉使ICa的穩(wěn)態(tài)激活曲線(xiàn)向超極化方向移動(dòng)大約9mV左右，但是對(duì)其穩(wěn)態(tài)失活動(dòng)力學(xué)沒(méi)有顯著影響。 結(jié)論：水楊酸鈉通過(guò)對(duì)海馬部位神經(jīng)元上的電壓門(mén)控性鈣通道的抑制作用，導(dǎo)致海馬神經(jīng)元的神經(jīng)遞質(zhì)的釋放減少，這可能是抑制性神經(jīng)遞質(zhì)減少的主要原因。而抑制性神經(jīng)遞質(zhì)減少后會(huì)導(dǎo)致神經(jīng)元過(guò)度興奮。 總結(jié)：水楊酸鈉對(duì)海馬部位神經(jīng)元IK(DR)的抑制作用（IC50為1.43mM）其對(duì)海馬神經(jīng)元ICa的抑制作用（IC50為1.64mM）其對(duì)海馬神經(jīng)元INa的抑制作用（IC50為2.07）其對(duì)海馬神經(jīng)元IK(A)的抑制作用（IC50為2.18mM）。水楊酸鈉改變IK(DR)的穩(wěn)態(tài)激活曲線(xiàn)和穩(wěn)態(tài)失活曲線(xiàn)，使其向超級(jí)化方向移動(dòng)；同時(shí)水楊酸鈉改變INa和ICa的穩(wěn)態(tài)激活曲線(xiàn)，使其向超級(jí)化方向移動(dòng)；但是水楊酸鈉對(duì)IK(A)的穩(wěn)態(tài)激活曲線(xiàn)和穩(wěn)態(tài)失活曲線(xiàn)均沒(méi)有影響。
[Abstract]:tinnitus is a kind of common auditory system disease , which is characterized by the presence of a ghostly ringing tone or beep in the ear without external corresponding sound source . The clinical doctor has noticed the relationship between tinnitus and emotional state . In recent years , it has been found that some related nuclei of the limbic system are involved in the formation of bad mood of tinnitus , such as the excessive amount of sodium salicylate can cause tinnitus , and it is an important tool for studying the mechanism of tinnitus . Effect of Sodium Salicylate on Voltage - gated Potassium Ion Channels in Hippocampus Neurons Objective : To observe the effect of sodium salicylate on transient outward potassium channel and delayed rectifier potassium channel in rat hippocampal neurons by using the technique of brain slice patch clamp . The changes of I - V curve , steady state activation curve and steady - state inactivation curve of IK ( A ) and IK ( DR ) were observed before and after administration of 1 mM sodium salicylate . RESULTS : Sodium salicylate inhibited IK ( A ) and IK ( DR ) and had a concentration - dependent effect . Sodium salicylate had no effect on the steady - state activation kinetics and steady - state loss of motion of IK ( A ) . However , the steady - state activation kinetics of IK ( DR ) and steady - state loss of activity were affected . 1 mM sodium salicylate shifted the steady - state activation curve of IK ( DR ) to a hyperpolarization direction of about 12 mV , and the steady - state inactivation curve shifted about 19 mV to the hyperpolarization direction . Conclusion : Sodium salicylate can prolong the duration of action potential , enhance the release of neurotransmitters , accelerate the repetitive discharge rhythm of neurons , and improve the excitatory properties of neurons by inhibiting the transient outward potassium channels and delayed rectifier potassium channels on the neurons of the hippocampus . Effect of Sodium Salicylate on Voltage - gated Sodium Ion Channels in Hippocampus Neurons Objective and Methods : We observed the effect of sodium salicylate on electrophysiological characteristics of voltage - gated sodium channel in rat hippocampal neurons by using the technique of slice patch clamp . The changes of I - V curve , steady - state activation curve and steady - state inactivation curve of INA were observed before and after administration of 1 mM sodium salicylate . RESULTS : Sodium salicylate inhibited INA ' s steady - state activation curve and its steady - state activation curve shifted to the hyperpolarization direction by about 10 mV , but it had no effect on the steady - state inactivation curve . Conclusion : The inhibitory effect of sodium salicylate on the voltage - gated sodium ion channel on the neurons in the hippocampus is reduced , the threshold of action potential is decreased , the neurons are excited , the neurons are excited , the repetitive discharge of neurons and the release of neurotransmitters are promoted . Effect of sodium salicylate on voltage - gated calcium channel in hippocampus neurons Objective and Methods : To observe the effect of sodium salicylate on the electrophysiological properties of voltage - gated calcium channel in rat hippocampal neurons by using the technique of slice patch clamp . The changes of I - V curve , steady - state activation curve and steady - state inactivation curve of ICa before and after administration of 1 mM sodium salicylate were observed . RESULTS : Sodium salicylate inhibited ICa and had a concentration - dependent effect . The steady - state activation curve of ICa moved about 9 mV to the hyperpolarization direction , but there was no significant effect on its steady state loss mechanics . Conclusion : The inhibitory effect of sodium salicylate on the voltage - gated calcium channel in the hippocampal neurons leads to a decrease in the neurotransmitter release in the hippocampus neurons , which may be the main reason for the decrease of inhibitory neurotransmitter . The inhibitory effect of sodium salicylate ( IC50 of 1.43mM ) on the neurons of hippocampus was inhibited ( IC50 = 2.07 ) . The inhibitory effect of sodium salicylate on the neurons of hippocampus ( IC50 of 2.07 ) was inhibited ( IC50 = 2.18mM ) . The steady - state activation curve and steady - state inactivation curve of IK ( DR ) were changed to move towards the super - direction ; however , sodium salicylate did not influence the steady - state activation curve and the steady - state inactivation curve of IK ( A ) .

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R764

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