Title

探討有無包覆F127之butylidenephthalide對於抑制老化鼠之神經退化的保護效果

Translated Titles

Investigating the effect of F127 coating on the butylidenephthalide-mediated neural protection in aged mice

Authors

黃逸軒

Key Words

阿茲海默症 ; 老化鼠 ; N-butylidenephthalide ; Aging mice ; N-butylidenephthalide

PublicationName

中興大學生命科學系所學位論文

Volume or Term/Year and Month of Publication

2018年

Academic Degree Category

碩士

Advisor

蘇鴻麟

Content Language

繁體中文

Chinese Abstract

阿茲海默症(Alzheimer’s disease, AD)為失智症主要病因,也是最常見的神經退化性疾病之一。在台灣105年官方統計中,65歲以上失智人口有24萬人,平均每13位老人就會有一位是失智者,為影響國人醫療、經濟與社會的重要議題。老化鼠 (senescence-accelerated mouse, SAM) 為研究老化疾病的動物模式,其中SAMP8小鼠,除了早發性的衰老外,同時大腦也會有大量的Amyloid beta (Aβ) 堆積形成斑塊,此現象與AD極為相似,因此經常作為研究AD的模式動物。而現今的治療方式只能減緩病程並無法完全根治,但延緩效果依然十分有限,因此近幾年科學家們偏向於去尋找相對較低生物毒性的天然食物或是中草藥萃取出的小分子藥物來治療AD。我們選用的Butylidenephthalide (Bdph) 為當歸的主要成分之一,在實驗室先前研究中將高分子物質F127包覆Bdph後,並餵食SAMP8小鼠200 mg/kg包覆F127之Bdph十九周後能改善記憶與學習障礙。因此本研究想探討有無包覆高F127的Bdph,對於SAMP8小鼠的行為及組織樣本分析的差異。首先將未滿八周齡之SAMP8小鼠,以主動穿梭迴避試驗進行篩選,區分為在主被動學習狀況良好(SM)及較差(ST)兩部分,並分別餵食有無包覆F127的兩種Bdph持續兩個月後,以莫里斯水迷宮 (Morris water maze)檢測小鼠記憶力衰退的情況。研究結果顯示,餵食F127-Bdph與單純餵食Bdph組相比有明顯較快找到平台,而且不管是在SM或是ST的組別中都具有相同的趨勢。後續以抽血檢測小鼠體內ROS、catalase及發炎因子IL-1β的濃度變化,最後進行海馬迴Aβ含量的檢測與大腦組織切片染色,部分實驗結果顯示F127-Bdph與Bdph原液相比具有較好的治療效果,包括減少腦部Tau蛋白過度磷酸化的情形,並增加神經的保護作用。因此F127-Bdph相較於Bdph原液更具有治療AD等神經退化性疾病的潛力。

English Abstract

Alzheimer’s disease(AD) is the most common neurodegenerative disorder. According to Taiwan's official statistics in 2016, there are 240,000 people over the age of 65 with dementia. An average of 13 elderly people will have one dementia patient. AD has become an important issue of medical economy and society. Senescence-accelerated mouse (SAM) is an animal model for studying aging diseases. Among the SAM mice, SAMP8 also has Amyloid beta (Aβ) accumulation in its brain. This phenomenon is very similar to Alzheimer's disease and is therefore often used as a model animal for studying AD. Current treatment can only slow down the course but unable to completely cure AD. And the delay effect is still very limited. Recently, researches prefer to use natural foods or Chinese herbal medicine with relatively lower biological toxicity of small molecule drugs to treat AD. Butylidenephthalide (Bdph) is one of the main components of Angelica sinensis. In our previous study, F127-coated Bdph was fed to SAMP8 mice at the dosage of 200 mg / kg for nineteen weeks. And results showed that this can rescue memory and learning disabilities. Therefore, our aim in this research is to investigate the effect of F127 coating on the butylidenephthalide-mediated neural protection in SAMP8 mice. SAMP8 mice younger than eight weeks were screened by an active shuttle avoidance test and then divided into good learning group(SM) and poor learning group(ST). Both group were fed with or without F127-coated Bdph respectively for two months. We chose Morris water maze to test for memory loss in mice. Feeding F127-Bdph was significantly faster to find the platform whether SM or ST groups, and both have the same tendency. Next, we tried to investigate ROS, Catalase and IL-1β concentration changes in mouse blood. And detect Aβ content in hippocampus and brain tissue sections staining. Part of results showed F127-coated Bdph had better effects than only Bdph, including reduce brain tau hyperphosphorylation, and increasing neuroprotective. Therefore, F127-Bdph has the potential of treating neurodegenerative diseases such as AD more than Bdp diluted with olive oil.

Topic Category 生命科學院 > 生命科學系所
生物農學 > 生物科學
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