臺灣博碩士論文加值系統

背景：睡眠呼吸中止症 (sleep apnea, SA) 是現今社會中非常普遍的疾病，約影響70%的人口。SA在睡眠中會出現間歇性缺氧 (intermittent hypoxia, IH)，造成發炎、睡眠中交感神經活化、睡眠片斷化及心血管問題等。過去研究顯示，SA患者罹患中風機率非常高。在動物實驗上發現IH會使血管硬化和加重局部腦缺血的傷害。目前較少研究探討SA對於中風造成之損傷其中自律神經功能及睡眠結構改變所扮演的角色。假設： IH期間會造成大鼠血壓及交感神經活性上升並使睡眠中斷次數增加及不穩定睡眠等，並會促使大鼠缺血型腦梗塞後傷害面積變大及行為受損，自律神經失調及睡眠不穩定。材料方法：Wistar Kyoto (WKY) 大鼠分為IH組及Air組。首先植入頭電極以紀錄及分析24小時睡眠及自律神經功能，術後休息一週後開始IH的介入。IH以每天8小時，5%的低氧濃度介入兩週，兩週後會施行中腦動脈梗塞 (middle cerebral artery occlusion, MCAO) 手術，當天休息後IH再介入一週，實驗結束將大鼠犧牲，取腦並作切片，將腦切片以2,3,5-氯化三苯四氮唑 (2,3,5-triphenyltetrazolium chloride, TTC) 染色做腦梗塞面積分析。實驗結果：(1) 跟Air組比，IH組會降低大鼠體重及飲食，提高安靜及奇異睡眠中的交感神經活性及奇異睡眠副交感神經活性；安靜睡眠時間減少、單次安靜睡眠發生持續時間下降、睡眠中斷增加。(2) 跟空氣Air組比，IH組在MCAO介入會使血壓上升，MCAO造成之腦部傷害更為嚴重，行為能力下降；IH組MCAO後與之前比，安靜及奇異睡眠時心跳間距變及交感神經活性下降，清醒、安靜及奇異睡眠時副交感神經活性下降，睡眠參數與MCAO前比並無顯著變化。(3) MCAO前介入IH的8小時期間，安靜睡眠及奇異睡眠中的交感神經活性提高與MCAO後大鼠移除異物時間增加呈正相關，整體及奇異睡眠交感神經活性提升與MCAO後之感覺能力變差呈正相關。結論：MCAO前IH造成之睡眠交感提升與MCAO造成動物行為缺陷有關，跟Air組比IH組在MCAO後交感及副交感神經活性會進一步的下降。本論文提出睡眠呼吸中止症可能會對後續中風造成更大的傷害，這些可能與睡眠呼吸中止發生期間的交感神活性過度興奮有關。提醒重視睡眠呼吸中止症及期間交感神經過度性奮的重要性。

Background: Sleep apnea (SA) is a common disease, is characterized by intermittent hypoxia (IH), lead to inflammation, sympathetic nerve activity (SNA) increasing, sleep fragmentation and carries an increased risk of cardiovascular events. Previous studies show that SA increases the risk of stroke. Furthermore, IH has been reported to cause arteriosclerosis and increase brain injury in animal models of focal cerebral ischemia. However, few researches investigating of the changing of cardiac-autonomic nerve system and sleep structure which IH lead to after stroke. Hypothesis: IH can lead to blood pressure (BP), SNA rising and increase sleep interruption. IH can also lead to more serious brain injury and behavior disability, autonomic nerve system imbalance and sleep unstable after stroke. Material and Methods: Wistar Kyoto rat (WKY) were divided into IH group and Air group. ECG, EMG and EEG were recorded for 24 hours. IH (hypoxia: 5% O2) was carried out 8 hours a day for 2 weeks. WKY were then subjected to a permanent right middle cerebral artery occlusion (MCAO). Continue exposing to IH for one week after MCAO. Results: (1) IH decreased weight and food intake, increased QS and PS SNA, increased PS parasympathetic nerve activity (PNA), decreased QS time and duration, increased sleep interruption. (2) After MCAO, IH led to BP increasing, more serious brain injury and poor behavior ability. IH increased heart rate, decreased SNA during QS and PS, decreased AW, QS, PS PNA. (3) During IH was carried out before MCAO, the increasing of QS and PS SNA is related to the increasing of removal time after MCAO. The increasing of total and PS SNA is related to the increasing of contact time. Conclusions: The increasing of SNA caused by IH before MCAO is related to worse brain injury after MCAO. The decreasing of PNA caused by IH before MCAO is related to worse sleep quality after MCAO. Improve the SA may help stroke patients to recover and sleep well.

致謝 i
中文摘要 ii
英文摘要 iv
第一章 背景介紹及文獻探討 1
1.1睡眠呼吸中止症 1
1.1.1間歇性缺氧動物模式 1
1.1.2間歇性缺氧對自律神經的影響 2
1.2腦部中風 3
1.2.1腦中風對心率及自律神經的影響 4
1.2.2睡眠呼吸中止症與腦中風 4
1.3心率變異性參數與自律神經系統 5
1.3.1大鼠的心率變異性頻譜分析參數 5
1.4腦波、腦波頻譜分析及睡眠 6
第二章 研究假設與目標 7
2.1研究假設 7
2.2研究目標 7
第三章 材料與方法 9
3.1 動物選擇與手術、實驗流程 9
3.1.1電極植入手術 9
3.1.2間歇性缺氧 (IH) 9
3.1.3中腦動脈梗塞手術 10
3.1.4 MCAO後所造成腦傷分析 10
3.1.5 行為測試及分析 11
3.2 生理訊號紀錄與處理 11
3.3 睡眠分析方法 12
3.4 心率變異之分析方法 13
3.4.1心電訊號處理 13
3.4.2心電訊號頻域分析 13
3.4.3頻譜分析判讀 14
3.5 統計分析 14
第四章 實驗結果 15
4.1 IH介入對各生理參數的影響 15
4.1.1體重、食物攝取量、飲水量、血壓及行為 15
4.1.2 心率變異性參數 15
4.1.3 睡眠結構 17
4.2 IH對MCAO引發生理參數的變化之差異 21
4.2.1腦部梗塞面積 21
4.2.2 體重、食物攝取量、飲水量、血壓及行為 22
4.2.3 心率變異性 22
4.2.4 睡眠結構 25
4.3 MCAO後行為與MCAO前IH介入期間生理參數相關性 29
4.4 MCAO後行為、腦梗塞傷害體積與MCAO前後生理參數變化之相關性 31
第五章 討論 32
參考文獻 35
附圖 45

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