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Title: | 大麻二酚在光誘導視網膜退化病變模式下的神經保護效果 Neuroprotective Effect of Cannabidiol in Experimental Light-induced Retinal Degeneration |
Authors: | Shih-Ting Huang 黃詩婷 |
Advisor: | 林中天(Chung-Tien Lin) |
Keyword: | 大麻二酚,視網膜退化,光傷害,神經保護, cannabidiol,CBD,retinal degeneration,light damage,neuroprotection, |
Publication Year : | 2009 |
Degree: | 碩士 |
Abstract: | 遺傳性視網膜退化症無論在人還是犬隻,到目前為止尚未有有效的方式可以
治癒,近年來的研究發現主要為視網膜感光細胞凋亡所造成,同時可能與微膠細 胞(microglia cells)過度活化有關。本研究利用光照曝露的方式誘導Sprague-Dawley 大鼠的視網膜病變,建立視網膜感光細胞凋亡的動物模式,用以研究遺傳性視網 膜退化症的病變,同時進行嘗試性的藥物治療,以供未來臨床治療上的另一考量。 本研究中選擇的藥物大麻二酚(cannabidiol, CBD)於之前的研究中曾被指出 具有抗氧化、抗發炎、以及神經保護的效果,並選擇已被發表於相同模式下具由 神經保護效果的minocycline 來做比較。在研究中利用視網膜電波圖以及組織病理 的型態變化來評估其具有的神經保護效果,此外進一步探討大麻二酚與微膠細胞 的活化關係,藉此確認大麻二酚達到神經保護效果的機制。結果發現以光誘導視 網膜病變的治療對照組在視網膜電波圖檢測下,比起正常大鼠有顯著的a 波以及b 波的振幅下降。組織病理檢查發現治療對照組之視網膜的外核層以及感光細胞層 厚度顯著的減少,同時外核層的細胞排列鬆散、並呈現空洞化。在免疫組織化學 染色偵測下發現,治療對照組在視網膜的外層有明顯的微膠細胞活化。研究發現 大麻二酚在視網膜電波圖以及組織病理的評估下,皆能減緩光誘導之視網膜病 變,並且抑制微膠細胞的活化,比起治療對照組有顯著差異。因此認為大麻二酚 具有神經保護效果。但在臨床上對於視力的實際保護效力未來仍需要更進一步的 評估。 Inherited retinopathy, progressive retinal atrophy(PRA), is a group of common inherited retinopathies in dogs. There is no treatment for inherited retinopathy to date. Loss of vision cells by apoptosis is a key feature of PRA. Microglia cells have been believed to play an important role in neurodegenerative diseases. Light-induced retinal degeneration has been a good experimental model to study the pathophysiology and therapeutic modalities in photoreceptor-led retinal degeneration. The purpose of this study was to evaluate the neuroprotective effect of cannabidiol(CBD)to investigate whether CBD can ameliorate light-induced retinal degeneration. Sprague-Dawley rats received an intraperitoneal injection of CBD, minocycline or vehicle 12 hours before exposure to white light. Morphologic, immunohistochemical, and scotopic electroretinograms were performed to evaluate the effect of CBD and the possible involvement of microglial cells. After exposure to light scotopic electroretinography showed that both the amplitude of a- and b-wave significantly reduced of the vehicle-treated group. Retinal histology revealed that the outer nuclear layer and outer segment of the retina were significantly decreased in vehicle-treated group, and OX42-positive microglia occurred in the ONL and subretinal space. The CBD-treated group showed markedly better preservation of retina electrophysiologically and morhologically after light damage, and significantly reduced the number of OX42-positive microglia than the vehicle-treated group. CBD may process neuroprotective effect against photoreceptor degeneration following light exposure based on this study, and possibly through the inhibition of retinal microglial activation. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/9382 |
Fulltext Rights: | 同意授權(全球公開) |
Appears in Collections: | 臨床動物醫學研究所 |
Files in This Item:
File | Size | Format | |
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ntu-98-1.pdf | 2.66 MB | Adobe PDF | View/Open |
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