臺灣博碩士論文加值系統

背景：過去發現正常血壓 (WKY) 母鼠會因壓力而使交感神經活性上升、副交感神經活性下降及類似失眠作用，而補充雌激素後可緩解此狀況；高血壓大鼠 (SHRs) 有較高的血壓與交感神經活性，及較低的副交感活性與感壓反射。雌激素對於母鼠WKY與SHR之作用是否相似或有相同成效仍然未知。假設：SHRs母鼠面對壓力造成的自律神經反應及失眠作用，較WKY來的明顯且雌激素會緩解此反應。本論文利用環境改變之壓力誘發失眠動物模式以比較去卵巢SHRs母鼠在有無補充雌激素之差異，並與WKY比較。材料與方法：動物組別分為 (1) SHR大鼠分成公鼠假手術 (SHR-Male)、母鼠假手術 (Sham-Female) 與去卵巢 (OVX) 三組；(2) 將WKY與SHR分為OVX+Oil及OVX+Estrogen兩組。手術以植入電極之方式以記錄和分析24小時睡眠與自律神經功能。術後休息10天，以交叉分配方式選擇更換三種不同環境（乾淨、自己和其他老鼠住一週的籠子）。結果：(1) SHRs與WKY的變化在公母的表現類似。(2) SHRs於安靜睡眠期會因為環境壓力而使血壓及心臟交感神經活性有明顯的增加，且皆高於WKY。同時可觀察到心跳間距及副交感神經活性的下降。(3) 與OVX+Oil相比，OVX+Estrogen組居住於三種環境時在光亮週期清醒時期有較高的副交感活性；在安靜睡眠時，則是特別在居住於他隻老鼠髒環境時才有較高的副交感活性。結論：WKY和SHR去卵巢後換dirty cage所引起的壓力皆會造成睡眠問題；但兩者相比，雖然SHR在去卵巢後的深睡時間雖較WKY多，但更加難以入睡，而給予雌激素僅可以讓去卵巢WKY減少入睡時間，而給予雌激素無法緩解SHR的睡眠問題。

Background: Our previous study implied that estrogen may overcome the stress induced-sleep disturbance in ovariectomized (OVX) WKY female rats. Spontaneously hypertensive rats (SHRs) have higher blood pressure and sympathetic activity, and lower parasympathetic activity and baroreflex sensitivity than normotensive Wistar-Kyoto rats (WKYs). However, it is still unknown whether estrogen also has the same effects in female SHRs. Hypothesis: 1. SHRs and WKYs show the different baseline values. 2. SHRs show the more obvious responses of stress-induced sleep disturbance and autonomic imbalance than those in WKYs. Material and methods: Animal groups: (1) Male and female SHRs were divided into three groups: Sham-Male, Sham-Female and OVX. (2) The female WKYs and SHRs were divided individually into two groups: OVX-Oil and OVX-Estrogen groups. Electroencephalogram, electromyogram, electrocardiogram, and blood pressure were recorded for 24 hours in three different cages (clean, dirty cages: occupied by self or another rat) by crossover design. Results: 1. WKYs and SHRs showed similar alterations of all parameters. 2. Cage-switch increased blood pressure and cardiac sympathetic activity but decreased R-R intervals and parasympathetic activity in SHRs during quiet sleep (QS) period, and these phenomena were more obvious than WKYs. 3. Compared with OVX-Oil group, the OVX-Estrogen group showed higher parasympathetic activity when living in three different cages in light period, especially when the rats lived in other’s dirty cage. Conclusions: Both OVX WKYs and SHRs have sleep problems in dirty cage-switch stress. When comparing both groups, OVX SHRs spend more QS time than OVX WKYs, but they have more severe difficulty falling asleep. Moreover, estradiol supplement can decrease sleep latency in OVX WKYs, but it can not improve sleep problems in OVX SHRs.

目錄 i
圖目錄 iv
Abstract vi
中文摘要 vii
研究背景介紹 1
壓力引發生理改變 1
睡眠問題 1
自律神經功能之變化 1
心血管疾病的誘發 2
性別差異 2
壓力誘導失眠的動物模式 2
雌激素之生理作用 3
睡眠之影響 3
心血管自律神經之調控 4
對壓力的影響 4
更年期女性議題 4
失眠問題與自律神經失調 5
過去實驗室的發現 6
自發性高血壓大鼠與正常血壓大鼠之差異 6
循環變異性參數與自律神經系統 7
腦波、腦波頻譜分析及睡眠 8
研究動機及假說 10
目標 11
重要性 12
研究方法與步驟 13
動物選擇與處理 13
動脈壓測量手術 13
卵巢去除手術 13
頭電極植入手術 14
雌激素補充方法 14
實驗流程 15
訊號收集 15
睡眠與自律神經分析方法 16
心電與血壓訊號處理 17
雌激素與壓力荷爾蒙濃度量測 19
統計分析 19
實驗結果 20
SHR 公鼠、母鼠和 OVX 母鼠之差異 20
光亮時的睡眠結構差異 20
光亮時的睡眠血壓及自律神經活性差異 21
光亮時的睡眠品質 21
睡眠前、後期的改變情形 21
光亮時的腦波變化 21
WKY 與 SHR 母鼠 OVX 補充溶劑 (OVX+Oil) 與雌激素 (OVX+E) 之差異
22
光亮時的睡眠結構差異 22
光亮時的睡眠血壓及自律神經活性差異 22
SHR 母鼠 OVX 補充溶劑 (OVX+Oil) 與雌激素 (OVX+E) 之差異 22
光亮時期的睡眠品質 22
光亮到光暗的睡眠 (QS) 改變情形 22
光亮時的腦波變化 23
壓力引發深睡時間減少之比例 23
雌激素濃度 23
討論 24
本論文之限制 27
結論 27
參考文獻 28
附圖 34


圖目錄
圖 1、單隻 SHR 公鼠 (Sham-Male)、母鼠假手術 (Sham-Female) 與母鼠去卵巢(OVX) 於壓力環境中之連續 24 小時的各種生理訊號原始圖
35
圖 2、假手術之 SHR 公鼠 (Sham-Male)、母鼠 (Sham-Female) 與去卵巢 (OVX) 後母鼠於四種鼠籠狀態下，光亮 12 小時的睡眠結構圖 37
圖 3、假手術之 SHR 公鼠 (Sham-Male)、母鼠 (Sham-Female) 與去卵巢 (OVX) 後母鼠於四種鼠籠狀態下，光亮 12 小時中的深睡狀態心血管自律神經活性改變 39
圖 4、假手術之 SHR 公鼠 (Sham-Male)、母鼠 (Sham-Female) 與去卵巢 (OVX) 後母鼠於四種鼠籠狀態下，光亮 12 小時中的睡眠品質差異
40
圖 5、SHR 公鼠、母鼠假手術 (Sham-Female) 與去卵巢 (OVX) 未更換環境(Baseline) 與更換至乾淨 (clean)、髒環境 (Dirty) 每兩小時平均睡眠 (QS)時間隨時間的改變情形 41
圖 6、假手術之 SHR 公鼠 (Sham-Male)、母鼠 (Sham-Female) 與去卵巢 (OVX) 後母鼠於四種鼠籠狀態下，光亮 12 小時中的腦波變化 43
圖 7、單隻 SHR 母鼠去卵巢並補充溶劑 (OVX+Oil) 和雌激素 (OVX+E) 後於壓力環境中之連續 24 小時的各種生理訊號原始圖 45
圖 8、WKY 與 SHR 母鼠去卵巢並補充溶劑 (OVX+Oil) 和雌激素 (OVX+E) 後於四種鼠籠狀態下，光亮 12 小時的睡眠結構圖 47
圖 9、WKY 與 SHR 母鼠去卵巢並補充溶劑 (OVX+Oil) 和雌激素 (OVX+E)後母鼠於四種鼠籠狀態下，光亮 12 小時中的深睡時心血管自律神經活性改變 49
圖 10、SHR 母鼠去卵巢並補充溶劑 (OVX+Oil) 和雌激素 (OVX+E) 後於四種鼠籠狀態下，光亮 12 小時中的睡眠品質差異 50
圖 11、WKY 與 SHR 母鼠去卵巢並補充溶劑 (OVX+Oil) 和雌激素(OVX+E) 後母鼠在未更換環境 (Baseline) 與更換至乾淨 (Clean)、髒環境 (Dirty) 每兩小時平均睡眠 (QS) 時間隨時間的改變情形 52
圖 12、SHR 母鼠去卵巢並補充溶劑 (OVX+Oil) 和雌激素 (OVX+E) 後於四種鼠籠狀態下，光亮 12 小時中的清醒狀態之腦波變化 54
圖 13、WKY 去卵巢後補充溶劑與雌激素與 SHR 公鼠、母鼠、去卵巢母鼠、去卵巢後補充溶劑與雌激素於髒環境 Dirty (other) 下與未更換環境 Baseline 的深睡時間減少比 55
圖 14、SHR 公鼠 (Sham-Male)、母鼠 (Sham-Female)、去卵巢 (OVX)、去卵巢後補充溶劑 (OVX+Oil) 和雌激素 (OVX+E) 血液中的賀爾蒙濃度
56

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