2011-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/645726摘要:近年來,鼓室內投予氨基苷類藥物,被廣泛用來治療美尼爾病之頑固性眩暈。對於突發性耳聾,亦有經鼓膜注射類固醇的治療模式;此外,對於急慢性中耳炎,何種新型的耳滴劑既有效又不致傷及內耳亦未明。這些新的治療模式不斷地推出,但耳毒性的評估僅賴傳統的聽力檢查及溫差測驗是不夠的。因為並無偵測到耳石器(球囊及橢圓囊)的毒性,造成有些病人將來會產生平衡失調,如良性陣發性頭位眩暈。最近,我們實驗室利用氣導音聲和骨導振動刺激,成功地在天竺鼠頸部肌肉上記錄到所謂的頸性前庭誘發肌性電位(cVEMP) ; 及在眼外肌上記錄到眼性前庭誘發肌性電位(oVEMP)。前者檢測未交叉的「球囊頸反射」,可反映球囊的訊息。後者評估已交叉的「前庭眼反射」,可偵測橢圓囊的功能。再輔以溫差測驗檢測半規管,及ABR 檢測耳蝸,時至今日,所有內耳的終末器官均可完整地受到監控。對於臨床上經鼓膜注射給藥的治療途徑,上述嶄新的內耳監控系統,包括ABR、溫差測驗、oVEMP 檢查、與cVEMP 檢查,可用來評估耳蝸、半規管、橢圓囊、及球囊的功能。故本三年期計畫包括,第一年計畫檢測 gentamicin 的耳毒性;第二年計畫檢測類固醇的耳毒性;第三年計畫檢測耳滴劑的耳毒性。檢查後,動物予以犧牲,再藉由光學顯微鏡及免疫螢光顯微鏡進行病理檢查。本計畫的最終目的,在利用上述嶄新的內耳監控系統,評估臨床上經由鼓膜注射的各種藥物之耳毒性,以杜絕不良反應的發生。<br> Abstract: It is well-known that aminoglycoside eardrops can combat the gram-negative bacterialinfection of the ear, but its toxicity is also noted with different susceptibilities in cochlear andvestibular sensory cells. Intratympanic gentamicin administration has become the preferredtreatment for intractable vertigo in cases of Meniere’s disease. While most studies haveidentified damage in the cochlea and semicircular canals as the primary sites ofaminoglycoside toxicity, little attention has been devoted to the effect on the otolithic organs.Recently, it has been established that cervical vestibular evoked myogenic potential (cVEMP)and ocular VEMP (oVEMP) can be elicited via air-conducted sound and bone-conductedvibration stimuli. The former assesses the ipsilateral sacculo-collic reflex; while the latterevaluates the crossed vestibulo-ocular reflex. Thus, all the inner ear endorgans can be easilyassessed via a sensitive monitoring system in guinea pigs and humans, which comprisesauditory brainstem response (ABR) for cochlear function, caloric test for the function ofsemicircular canals, ocular vestibular evoked myogenic potential (oVEMP) and cervicalVEMP (cVEMP) tests for assessing the functions of utricle and saccule, respectively. Thus,this monitoring system provides thorough toxicity information on the inner ear endorgans,assisting in the assessment of intoxication of various kinds of drug via an intratympanic route.Hence, this project administered gentamicin (first year), steroid (second year) and terbinafineeardrops (third year) directly onto the round window membrane of the guinea pigs,respectively, for investigating the toxic effects of various kinds of drug on the inner earendorgans via a sensitive monitoring system combined with morphological study.頸性前庭誘發肌性電位眼性前庭誘發肌性電位天竺鼠耳蝸半規管橢圓囊球囊ocular vestibular evoked myogenic potentialutricleAssessment of Ototoxicity for Various Kinds of Drug via an Intratympanic Route