聽力損傷是常見的感官障礙之一，而耳蝸缺血則是造成聽損的主因；許多聽力疾患如老年性聽障、噪音聽損或突發性耳聾等皆與耳蝸缺血有關，然而目前仍無有效的藥物來治療這類缺血性聽損。由於動物模式建立的困難，耳蝸缺血的完整基礎研究仍然很少；最近我們建立了暫時阻斷內耳迷路動脈的動物模式，並利用耳蝸細胞株培養，特提出一個對內耳缺血的完整基礎研究計畫；並藉此建立的細胞與動物模式，進而探尋耳蝸缺血性損傷可能有效的中草藥萃取物。本計劃為三年期： 第一年：利用已建立的細胞培養與耳蝸缺血動物模式，探討耳蝸細胞在暫時性缺血後的經時變化與死亡型態，進而探討其分子機轉變化。主要將採取(1)觀察耳蝸缺血時內耳的型態變化；(2)檢驗各類抗氧化酵素的變化情形；(3) 探討細胞凋亡或壞死的可能分子路徑，及(4)與缺血相關的誘發因子。 第二年：先期研究我們發現銀杏萃取物(EGb761)可緩解缺血對耳蝸的傷害，將進一步確認EGb761對於耳蝸缺血的時間窗研究，並配合耳蝸細胞株，探討其可能的分子機制。 第三年：基於上述結果與經驗，以耳蝸細胞培養模式作為藥物篩檢平台，篩選可能對耳蝸缺血性損傷有效的中草藥萃取物如黃耆、人蔘、兒茶素等，並在動物模式下驗證其效果，進而探討其可能的機轉。
Hearing loss is a common sensory deficit in human beings. Cochlear ischemia has been implicated to be the causative factor in the common auditory disorders such as presbyacusis, noise trauma or sudden deafness. However, there are no still effective neurotherapeutic interventions for these ischemia-related hearing losses. Because of technical difficulties, there are still few thorough researches to investigate the cellular events after cochlear ischemia. Recently, we have set up a chronic animal model of selective cochlear ischemia by transient occlusion of labyrinthine artery using microclamps. The aim of this project is to undergo a comprehensive basic investigation to the cochlear ischemia by virtue of our animal model and the cochlear hair cell culture technique. The ultimate goal is to search some potential drugs from the Chinese herbal extracts to treat the ischemia-related hearing losses. We plan to spend three years to complete this study. In the first year: We plan to investigate the dose and time responses of cochlear ischemia in vivo. The functional and morphologic changes as well as the cell death form after cochlear ischemia will be investigated in details. The cellular changes, especially the oxidative stress and signaling molecules involving ischemia and cell death, will be elaborated. In the second year: Our preliminary study showed that the Gingo biloba extract (EGb761) may have therapeutic effect for transient cochlear ischemia. We will further clarify the therapeutic time window for the EGb761 on different durations of cochlear ischemia. The detailed molecular mechanism will be investigated by virtue of the in vitro model. In the third year: According the results of the above, we will use the in vitro model as a platform for screening some Chinese herbal medicines for cochlear ischemia. For example, several common drugs known to be effective for ischemic neuropathy such as Huangqi (Astragalus) extract, Ginsenoside or Epigallocatechin gallate will be tried in vitro. Further effects of possible effective medicine and its possible molecular mechanisms will be justified both in vivo and in vitro.
