【作者】 郭振；

【导师】 汤正权； 李耕林；

【作者基本信息】 安徽大学 ， 生物学， 2024， 硕士

【摘要】 水杨酸钠是上广泛应用的一种临床场合水杨酸类药物,可以复方形式与其他镇痛药配制用以镇痛,对于风湿疾病亦为首选镇痛及诊治手段。然而,水杨酸钠对听觉系统具有一些毒副作用,临床上主要表现为耳鸣和听力减退。广泛的前沿临床基础医学研究表明,可靠且固定的诱导出耳鸣样行为,常在动物上超过一定程度剂量水杨酸钠的使用后诱发。以往的医学临床和基础研究工作表明,水杨酸钠作用于听觉外周耳蜗是诱导耳鸣主要原因。近来临床和基础研究结果也证明水杨酸诱导的中枢神经系统功能改变也是诱发耳鸣的原因之一。然而,目前人们对水杨酸钠在听觉中枢中的作用靶点尚不完全清楚。耳蜗核是耳鸣发生或维持的重要的脑区之一。本研究采用脑片膜片钳全细胞记录小鼠前腹侧耳蜗核主神经元丛细胞(Bushy cell,BC),探究了水杨酸钠对丛细胞的兴奋性的作用。在电流钳记录模式下,我们首先记录了C57小鼠前腹侧耳蜗核丛细胞的电生理特性,检测了水杨酸钠对于小鼠前腹侧耳蜗核神经元的直接作用。研究发现,水杨酸钠能直接导致前腹侧耳蜗核BC动作电位的阈值电流下降,动作电位波形变窄。此外,我们研究发现水杨酸钠还分别显著抑制钾电流和钠电流。为了进一步研究水杨酸钠对前腹侧耳蜗核神经元兴奋性改变的影响,我们检测了水杨酸钠对BC上的兴奋性突触后电流的作用。在电压钳模式下,全细胞记录BC,记录可编程脉冲刺激器电刺激耳蜗核区域传入神经的诱发兴奋性突触后电流。水杨酸钠不改变丛细胞的短时程突触可塑性,但是显著性抑制了诱发兴奋性突触后电流。根据以上实验结果,我们得出结论,水杨酸钠能降低耳蜗核丛细胞的动作电位阈值,以及抑制突触后电流(EPSCs),并推测这一影响打破了听觉中枢神经兴奋性和抑制性的平衡,进而可能诱导耳鸣发生。以上结果扩展了我们对水杨酸钠引发诱导耳鸣发生机制的进一步理解,并为将耳鸣诱发及成因等神经学研究提供了理论和科学基础。更多还原

【Abstract】 Sodium salicylate is a widely used drug in clinical practice.It contains salicylic acid and has pain relief,anti-inflammatory,and anti-platelet aggregation effects.However,sodium salicylate has some toxic effects on the auditory system,clinically manifested as tinnitus and hearing loss.A significant number of fundamental studies have demonstrated that high doses of sodium salicylate can also trigger tinnitus in animals.Numerous previous studies have demonstrated that sodium salicylate acting on the auditory periphery of the cochlea is the primary cause of inducing tinnitus.Recent clinical and basic studies have also proven that the changes in central nervous system function induced by salicylic acid are also one of the causes of tinnitus.However,the targets of sodium salicylate in the auditory center are not fully understood.The cochlear nucleus is one of the important brain regions involved in the occurrence or maintenance of tinnitus.In this study,patch-clamp whole-cell recordings of Bushy cells(BCs)in the mouse anterior ventral cochlear nucleus were conducted to examine the impact of sodium salicylate on the excitability of BCs.In this study,we initially recorded the electrophysiological characteristics of the cells in the anterior ventral cochlear nucleus of C57 mice under current clamp mode and examined the direct effects of sodium salicylate on the neurons in the anterior ventral cochlear nucleus.It was found that sodium salicylate could directly cause a decrease in the current threshold of the BC action potential in the anterior ventral cochlear nucleus and a narrowing of the action potential waveform.In addition,we found that sodium salicylate significantly inhibited potassium and sodium currents,respectively.To further investigate the effects of salicylate on the excitability of neurons in the anterior ventral cochlear nucleus,we examined the excitatory post-synaptic currents(EPSCs)in the BC.In voltage-clamp mode,the BC was recorded whole-cell,and evoked excitatory post-synaptic currents(e EPSCs)were recorded in response to electrical stimulation of the auditory nerve.Sodium salicylate did not alter short-term synaptic plasticity in bushy cells but significantly inhibited the e EPSCs.Based on the above results,we conclude that sodium salicylate can reduce the action potential threshold of cochlear bushy cells and inhibit postsynaptic currents(EPSCs),which disrupt the balance of excitability and inhibition in the auditory central nerve,ultimately leading to tinnitus.These results expand our understanding of the mechanism of salicylate-induced tinnitus and provide a theoretical and scientific basis for neurological studies on the induction and causes of tinnitus.更多还原