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研究生:黃千芝
研究生(外文):Chien-Chi Huang
論文名稱:自由活動小鼠睡醒狀態與心臟自主神經功能的關係
論文名稱(外文):The Association of Sleep-Wake States and Cardiac Autonomic Function in Free Moving Mice
指導教授:郭博昭郭博昭引用關係
指導教授(外文):Terry B. J. Kuo
學位類別:碩士
校院名稱:慈濟大學
系所名稱:神經科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2006
畢業學年度:94
語文別:中文
論文頁數:67
中文關鍵詞:光照週期自主神經弁�心率變異性睡眠小鼠
外文關鍵詞:light-dark cycleheart rate variabilityautonomic functionMicesleep
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我們實驗室研究指出,無論是在人類或大鼠的研究都顯示自主神經活性會隨著睡眠不同分期的轉換而變動,且這些變動出現異常可能與某些疾病有關。近年來,轉殖基因小鼠已被廣泛的應用在多種研究上,藉由基因工程的探索,已建立多種疾病的小鼠動物模式。過去在小鼠上收集生理訊號有不少限制,難以有效的了解小鼠睡眠清醒狀態與心臟自主神經功能的關係。本論文嘗試去建立一個適合研究睡眠時心臟自主神經功能的變化之自由活動小鼠模式,並探討光亮和光暗期是否對小鼠睡眠型式與心臟自主神經功能有所影響。
本論文利用多頻道睡眠記錄儀,連續記錄及分析非麻醉下自由活動小鼠之腦波、肌電波及心電波二十四小時,並以腦波與肌電波訊號進行睡眠分期之判讀。心電波則用來進行心率變異性頻譜分析,其參數包括心跳間距 (RR),總功率 (TP)、高頻功率 (HF) 與低頻 (LF) 對高頻的比值 (LF/HF),比較小鼠於清醒、安靜睡眠、奇異睡眠各睡眠分期的變化。
研究結果顯示,小鼠自主神經活性會隨著睡眠清醒狀態的改變而有所變動,與過去本實驗室已發表在人及大鼠上的結果相似。於安靜睡眠時,常伴隨著心跳間距、總功率、高頻功率的增加,低頻對高頻的比值減少與清醒時比較。相較於清醒,安靜睡眠時其低頻對高頻的比值減少,且與腦波的delta功率呈現負相關。於光暗期,小鼠各個睡眠分期所累積的時間,與光亮期比較,清醒時較安靜睡眠長,且心跳間距、高頻功率在各個睡眠分期都有顯著降低的現象,但低頻對高頻的比值於安靜睡眠和奇異睡眠則較高。
綜合上述,無論是人、大鼠或是小鼠,其睡眠時心臟自主神經功能的變化是相似的,故本論文建立一個研究睡眠清醒狀態與心臟自主神經功能之小鼠模式,期望未來能與分子生物學接軌。
Our laboratory has demonstrated that autonomic activation will changed with the alternation of sleep stages whether it is in human or rat, and that disregulatory of their activities may be related to certain diseases. Recently, due to the genetic transplanting into mice has been widely applied in several researches. Based on the exploring made by genetic engineering, many mice modes in diseases have been established. There were several constrictions in collecting physiological signals in mice in the past, which made understanding the association of sleep-wake states and cardiac autonomic function inefficient. In this study, we attempted to establish an applicable free moving mice model for investigation of sleep-wake related cardiac autonomic changes, and to explore whether there were any differences between light and dark periods throughout a day, and such differences were associated with sleep pattern and sleep-related cardiac autonomic function.
All mice were had electrodes implanted for polysomnographic recordings. Continous power spectral analysis of encephalogram (EEG), electromyogram (EMG), and electrocardiogram (ECG) were performed in unanesthetized free moving mice during 24-h diurnal cycle. EEG and EMG use to define the sleep-wake cycle. Frequency domain analysis of the stationary R-R intervals (RR) was perfored to quantify the total power (TP), the high-frequency power (HF), and the low-frequency power (LF) to HF ratio (LF/HF) of heart rate variability. Differences among active waking (AW), quiet sleep (QS), and paradoxical sleep (PS) were compared.
Being similar to our previous findings in humans and rats, mice have also revealed vigorously changes of cardiac autonomic functions along with the changes of sleep-wake states. QS stage was also coincidently accompanied with evidential increase in RR, total power and HF, but decrease in LF/HF as compared with the AW stage. Like humans and rats, LF/HF of mice also negatively correlated with the magnitude of the δ-power of EEG during QS stage. As compared with light period, the accumulated time was longer at AW stage and shorter at QS stage in dark period. The RR and HF in dark period was significantly lower than those in light period during each stage, but LF/HF during QS and PS stage was highter.
Our results showed that mice have the similar sleep-related autonomic changes as humans and rats. And this study also establishes a mouse model for molecular biologist to apply for evaluating the sleep-wake states and cardiac autonomic functions.
目錄
致謝………………………………………………………………….……………I

中文摘要…………………………………………………………..……….…III

英文摘要……………………………………………..…………….………..…V

目錄…………………………………………………………....….…....…VII

研究背景介紹……………………………………………..……..………...…1
小鼠動物模式對人類疾病研究之貢獻………………………….……………..1
研究睡眠-清醒與心循環自主神經變化之重要性…………….…..………….3
日變週期對睡眠及自主神經功能的影響…………………….…..…………..5
睡眠生理學……………………………………………………...……………..6
心率變異性與心臟自主神經活性…………………………...………………..8
心率變異性頻譜分析與心血管疾病的關係………………….……………….11

研究動機與目的……………………………………….…….....………..…13
研究動機…………………………………………………………..……………13
目的………………………………………………………………..……………13

研究材料與方法……………………………………………..……....……..14
實驗動物……………………………………………..…………….….……..14
腦波及心電電極植入手術………………………..…….…………….……..14
動物分組及設計…………………………………..…….…..……….………15
實驗流程……………………………………………..….…………….……..15
實驗器材……………………………………………..….……………...……15
資料收集……………………………………….………..……………...……16
心電訊號處理…………………………………….……..……………...……16
頻域分析………………………………………….….………….……...……17
睡眠型式分析………………………………………..…….…………...……18

統計分析…………………………………………...……………………...…19

研究結果……………………………………………..…………………..……20
睡眠清醒時自主神經功能的變化…………………..…….…………….…..20
睡眠深度與自主神經功能的變化…………………..…….…………….…..21
光亮-光暗週期對睡眠型式及睡眠腦波的影響…………….…….…….…..21
光亮-光暗週期對心臟自主神經功能的影響………….………………..…..22

綜合討論………………………………………………….……..…………...23
動物選取……………………….…………………………………....….....23
手術及記錄方法…………………..…………………………..……………..24
心率變異性頻率範圍之訂定……………………...……….……………....24
睡眠對自主神經功能的影響……………………...………...………………24
睡眠深度與自主神經功能的變化………………...……...……………....25
光亮-光暗週期對睡眠型式及睡眠腦波的影響...…………..………………26
光亮-光暗週期對自主神經功能的影響…………………...…..……………26
本研究之檢討……………………………….………………….………………27
動物分組選取…………………………….………………………..………...27
電極植入手術…………………………………………..…………………....27
電腦程式分析………………………………………….…….…………...….28
未來展望…………………………………………….………………………….28

結論……………………………………………...……………………….…..30

附表……………………..………………………………………….…….…..31

附圖……………………..………………………………………….………….33

參考文獻…………………………………………………………………..…..50
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