Aubert A, Bernard C, Clauser P, Harpey C, Vaudry H
Groupe de Recherche en Endocrinologie Moléculaire, CNRS URA 650, Unité Affiliée INSERM, Université de Rouen, Mont-Saint-Aignan, France.
Ann Otolaryngol Chir Cervicofac. 1990;107 Suppl 1:28-35.
Improvement of cochleovestibular symptoms induced by trimetazidine (TMZ) has been evidenced by clinical studies. However, a poor knowledge of the physiopathology and the scarcity of experimental models contributed to making determination of the mode of action of the drugs difficult. We studied the effect, in vitro, of TMZ on the production of oxygen-derived free radicals using, as a biological model, the isolated semicircular canal of the frog. This model allows to exert separate control over the ionic composition of the endo- and perilymphatic fluids. The spontaneous activity of the afferent nerve fibers, as well as the endolymphatic potential, were recorded at rest. Three additional parameters were analyzed, while the semicircular canal was subjected to mechanical stimulation, i.e., ampulla potential, nerve potential and the evoked frequency of action potentials. Free radical generation induced by the administration of phenazine methosulfate (PMS, 10(-5) M, 15 min) into the perilymphatic compartment, leads to a deterioration of the production of endolymph and the release of this afferent neuromediator. Inversely, PMS has no influence whatsoever on the mechanisms of mechanical-electrical transduction. The addition of TMZ (10(-6) or 10(-5) M) in the perilymphatic compartment counteracts the harmful effects of free radicals on the various bioelectric activities. These results suggest that the beneficial action of TMZ observed during treatment of cochleovestibular disorders is due, at least in part, to the anti-oxidizing properties of the molecule of interest.
临床研究已证实曲美他嗪（TMZ）可改善耳蜗前庭症状。然而，由于对其生理病理学了解不足以及实验模型匮乏，使得确定该药物的作用方式变得困难。我们以青蛙分离的半规管作为生物学模型，在体外研究了TMZ对氧自由基产生的影响。该模型能够分别控制内淋巴液和外淋巴液的离子组成。在静息状态下记录传入神经纤维的自发活动以及内淋巴电位。在对半规管进行机械刺激时，分析另外三个参数，即壶腹电位、神经电位和动作电位的诱发频率。向外淋巴腔注射吩嗪硫酸甲酯（PMS，10⁻⁵ M，15分钟）所诱导的自由基生成，会导致内淋巴生成以及这种传入神经介质释放的恶化。相反，PMS对机电转换机制没有任何影响。向外淋巴腔添加TMZ（10⁻⁶或10⁻⁵ M）可抵消自由基对各种生物电活动的有害影响。这些结果表明，在耳蜗前庭疾病治疗过程中观察到的TMZ的有益作用至少部分归因于该相关分子的抗氧化特性。
