臺灣博碩士論文加值系統

背景：由24小時動態血壓量測 (ambulatory blood pressure monitoring) 的結果發現，健康受試者於睡眠中會出現血壓下降之現象，而此下降的程度過低或消失與終端器官損傷 (target organ damage; TOD) 及心血管相關疾病的發生息息相關。一般認為日夜變化或醒睡轉換是血壓下降的主要之原因，其中自主神經系統於血壓調控及醒睡轉換中都扮演重要的角色。目的：建立血壓下降之動物模式，並利用此模式對血壓下降及不降現象作詳細之探討。以期能對相關疾病之機轉及治療有所進展。假說：觀察大鼠是否具有與人類類似之血壓下降及不降之現象，探討日夜變化及醒睡轉換對血壓下降幅度之影響，並試圖找出其可能之生理機轉。材料與方法：連續記錄正常血壓或高血壓大鼠24小時之血壓變化，根據不同光照週期其醒睡分期後比較光暗清醒與光照安靜睡眠時的血壓變化及相關生理參數之變化。結果：發現大鼠與人類相同也具有週期性的血壓變化，可再將大鼠依自訂之血壓下降準則區分為血壓下降 (dipper) 及血壓不降組 (non-dipper)。在兩組大鼠中都可發現醒睡轉換造成血壓下降之現象，而血壓不降組與下降組相比，在光亮時心跳間距 (RR) 未出現明顯增加及光暗時血管低頻功率 (BLF) 過低之現象。此外，在正常血壓大鼠中，光亮安靜睡眠時的正常化低頻功率 (LF%) 與血壓下降之幅度呈現顯著負相關。結論：不論正常血壓或高血壓大鼠都跟人類相似具有血壓下降及不降之現象，而醒睡轉換的影響可能是大鼠血壓下降之主因，但日夜變化之異常可能是造成大鼠血壓不降之原因。此外，於光亮安靜睡眠時的心臟交感神經活性過高可能是造成血壓不降的可能因素之一。

Background: 24 h ambulatory blood pressure (BP) monitoring present BP dipping pattern during sleep in healthy subject. The extent of the BP decline is highly correlation with target organ damage (TOD) and cardiovascular disease. Circadian rhythm and sleep-wake cycle are the two factors causing BP dipping. Autonomic nervous system plays a major role in BP regulation and sleep cycle change. Aims: Building a BP dipping animal model, which is useful for studying the mechanism of BP dipping. Hypothesis: We hypothesis that Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) would have BP dipping and non-dipping pattern. We aim to investigate effects of circadian rhythm and sleep-wake cycle on BP dipping in rats. Finally, we attempt to find the possible reason which causes dipping and non-dipping pattern in BP. Materials and Methods: 10-11 week-old WKY and SHR were used. One week after the electrode and telemetry transmitter implantation, blood pressure, electroencephalogram, electromyogram and electrocardiogram were continuously recorded for 24 hours in freely moving rats. Sleep-wake stage was defined using electroencephalogram electromyogram power spectrum, as active waking (AW), quiet sleep (QS), paradoxical sleep (PS). BP dipping was defined as the BP difference between light phase QS and dark phase AW. Rats were divided into dippers and non-dippers according to the amount of BP difference (>10% or <10% decline). BP and autonomic function were compared between two groups. Comparisons between two groups were tested by independent t test, and relationships between two sets of variables were measured by the linear regression analysis. Results: We found that rats have diurnal rhythm in BP like human. The effect of sleep-wake change caused BP dipping in rats. Compared with dippers, RR interval increase was not found during light period in non-dippers. In addition, QS LF% during light period was correlated with the amount of BP difference in WKY. Conclusion: We establish an animal model for BP dipping in rats. The possible mechanism of dipping pattern is sleep-wake change. However, abnormal circadian rhythm would cause non-dipping pattern in rats. Higher QS cardiac sympathetic activity during light period is a risk factor of non-dipping pattern.

目錄 i
中文摘要 iii
英文摘要 iv
研究背景介紹 1
24小時動態血壓量測與高血壓之定義 1
血壓下降與不降之定義 2
Non-dipping與心血管相關之疾病 2
Non-dipping對於心血管疾病之預後及治療之影響 3
Dipping and non-dipping之可能原因 4
目的 5
重要性 5
研究假說 6
研究材料與方法 7
實驗動物處理與實驗流程 7
大鼠BP dipping之定義 7
生理無線遙測系統電極植入手術操作 8
血壓電極埋設手術 9
生理訊號收集 9
生理訊號分析 10
睡眠分析 10
心率變異性及動脈壓變異性分析 11
頻譜分析結果判讀 11
感壓反射靈敏度評估 12
統計分析 12
實驗結果 13
建立BP dipping之動物模式 13
醒睡分期及光照週期對正常血壓大鼠WKY生理參數之影響 13
醒睡分期及光照週期對正常血壓大鼠WKY自主神經相關參數之影響 15
正常血壓大鼠WKY自主神經調控功能與BP dipping之相關性 16
感壓反射靈敏度對正常血壓大鼠BP dipping之影響 16
不同血壓下降程度之正常血壓大鼠在睡眠結構之比較 17
醒睡分期及光照週期對自發性高血壓大鼠SHR生理參數之影響 17
醒睡分期及光照週期對自發性高血壓大鼠SHR自主神經相關參數之影響 18
自發性高血壓大鼠SHR自主神經調控功能與BP dipping之相關性 18
討論 20
本論文之發現 20
此動物模式與人類之異同 20
此動物模式之優缺點 21
造成血壓下降現象之可能原因 21
造成血壓不降現象之可能原因 22
睡眠品質之參數對大鼠血壓下降模式之影響 23
本論文之限制及將來研究延續 23
結論 24
附圖 25
附表 48
參考文獻 51

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