使用果蠅動物模式探討麻醉藥物對退化性神經疾病的影響

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Title:	使用果蠅動物模式探討麻醉藥物對退化性神經疾病的影響 Using Drosophila Animal Model to Investigate the Effects of Anesthetics on Neurodegenerative Diseases
Authors:	陳嘉雯;Chen, Chia-Wen
Contributors:	臨床醫學研究所碩士班
Keywords:	吸入性麻醉藥;果蠅模式;阿茲海默氏症;β澱粉樣蛋白;Sevoflurane;Drosophila;Alzheimer’s disease (AD);β-amyloid protein (Aβ)
Date:	2012-07-26
Issue Date:	2012-08-31 16:35:27 (UTC+8)
Publisher:	中國醫藥大學
Abstract:	全球每年有超過兩億人接受手術，其中大部分又以使用吸入性麻醉藥(如sevoflurane等)之全身麻醉為多數，雖然這些吸入性麻醉藥被認為是安全且有效的，但近年來越來越多研究顯示有些病人會在手術後出現認知功能障礙甚至影響到學習與記憶功能，而其中又以老年人居多且症狀也比較嚴重，因此使用吸入性麻醉藥進行全身麻醉並非是沒有風險的。吸入性麻藥目前已在細胞及動物實驗上發現會對神經細胞造成傷害，藉此推測會影響到學習記憶功能。隨著人口老化，退化性神經疾病在全球有逐年逐漸增加的趨勢，其中又以阿茲海默氏症占大多數。阿茲海默氏症病因不明，主要是腦部神經退化且病理學上呈現β-澱粉樣蛋白的堆積，隨著病情的加重，病人的語言、認知、空間辨識能力及記憶會漸漸衰退。截至目前的研究多數是藉由吸入性麻醉藥對神經細胞造成發炎或凋亡反應去推測其會影響到學習、認知或記憶功能，但直接使用多次吸入性麻醉藥暴露-退化性神經疾病發病時間及症狀嚴重性的行為觀察卻尚未有任何報告。本研究之目的是利用果蠅模式其生活周期短、易於大量繁殖且與人類的基因有百分之七十七的同源性等特點，在多次吸入性麻醉藥Sevoflurane暴露後，觀察其退化性神經疾病-阿茲海默氏症發病狀況，包含爬行能力、視網膜光反射及存活率等。結果顯示：一、視網膜電圖：Sevoflurance暴露後可使阿茲海默氏症基因轉殖果蠅之光反射反應，由原先較正常果蠅減弱的情形回復至趨近正常，而對於正常的果蠅則沒有影響；二、爬行能力：阿茲海默氏症基因轉殖果蠅的爬行能力較正常果蠅差，Sevoflurance暴露後對於正常果蠅或阿茲海默氏症基因轉殖果蠅爬行能力皆沒有影響；三、存活率：阿茲海默氏症基因轉殖果蠅的存活時間較正常果蠅短，Sevoflurance暴露後對於正常果蠅或阿茲海默氏症基因轉殖果蠅之存活能力皆沒有明顯影響。因此，由我們的實驗發現吸入性麻醉藥Sevoflurane對正常及阿茲海默氏症基因轉殖果蠅之爬行能力及存活率沒有影響，對於視網膜光反射能力在阿茲海默症基因轉殖果蠅上可能具有保護作用。由我們的實驗觀察推測，Sevoflurane對於神經細胞不一定會造成傷害，且使用吸入性麻藥Sevoflurane進行全身麻醉可能安全且有效的。未來再針對果蠅腦部蛋白質變化的分析、神經細胞凋亡、及發炎反應，與果蠅的行為觀察作對應。 More than 200 million people undergo surgery annually worldwide, most of which is carried out under general anesthesia using inhaled anesthetics such as sevoflurane. Although these anesthetics are considered to be generally safe and effective, several studies have implicated them in postoperative cognitive decline. Hence, general anesthesia is not without risk. There are more evidences of cells and rodents suggesting that inhaled anesthetics could damage neurons. It supposes that general anesthesia would destroy learning and memory, including developing and senescent brain. The incidence of neurodegenerative disease increases with aging. Be again known as the majority of Alzheimer’s disease (AD) among them. AD is the most common form of dementia among older people and it affects a person’s ability to carry daily activities, like cognitive function, learning, and memory. The cause of AD is not well known; aging is the major risk factor. Brain amyloid plaques, which are deposits of β-amyloid protein is a neuropathological marker of AD. Drosophila model is used for many human diseases including AD. More than 77% of known human genes are recognizable match in the genome of Drosophila. Besides, cheap, short life cycle, and easily in great quantities breed are also the advantages of Drosophila model in neurodegenerative disease research. Up to now, the researches about neurotoxicity of inhaled anesthetics were indirect evidences. Most biological experiments of cell and animal supposed that general anesthesia might produce neurotoxicity and permanent cognitive impairment. The aim of this study is to investigate the neurologic effects of general anesthesia on AD transgenic Drosophila after inhaled anesthetics exposure. Climbing ability assay, electroretinagram (ERG), survival rate analysis were performed to observe the inhaled anesthetics impact on neurodegenerative diseases, such as AD. The results showed that the ERG of AD-transgenic Drosophila was reversed after sevoflurane exposure. There was no effect of sevoflurane on the ERG of wild-type Drosophila. The climbing ability of wild-type and AD-transgenic Drosophila were not affected after sevofluane exposure. The survival analysis of wild-type and AD-transgenic Drosophila were also not affected after sevoflurane exposure. Sevoflurane might not affect the climbing ability and survival of wild-type and AD-transgenic Drosophila. Sevoflurane might have protective effect on the retina function of AD-transgenic Drosophila. Therefore, sevoflurane may not have neurotoxicity on neurons and using inhaled anesthetics for general anesthesia may be safe and effective. The biological assay of neuron apoptosis, brain Aβ protein analysis, and inflammatory experiments will be performed in the future work to compare the results of motor functions of inhaled anesthetics on Alzheimer’s disease.
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