臺灣博碩士論文加值系統

中文摘要
從先前研究中了解心臟及其自主神經調控機制會分別受到日變週期及睡眠分期的影響，但對日變週期及睡眠型態兩者的相互作用卻不甚了解。本論文主要目的是利用自由活動之動物模式長時間觀察光照週期改變對於睡眠型態調節作用及睡眠相關自主神經活性變化情形。利用正常血壓大鼠 (WKY) 及高血壓大鼠 (SHR) 裝設多功能生理記錄電極，連續24小時記錄大鼠腦電波 (EEG)、肌電波 (EMG) 及心電波 (ECG) 訊號，區分光亮時 (light period) 與光暗時 (dark period) 睡眠型態及睡眠相關自主神經活性之變化。發現正常血壓大鼠在光暗時呈現醒多睡少的情形，且安靜睡眠中腦電波的d頻域之功率及所佔百分比也較少，平均每時期及每分鐘被干擾的情形也較多。至於在光暗時心率變異性變化，在安靜睡眠時R-R間距減少、高頻功率下降及低頻對高頻比值上升的現象。至於高血壓大鼠也有類似的光亮時與光暗時的差異。但與正常血壓大鼠相比較，高血壓大鼠在光亮時會有醒多睡少情形，安靜睡眠中腦電波的d頻域之功率及所佔百分比也較少，平均每時期及每分鐘被干擾的情形也較多。但在光暗時高血壓大鼠則與正常血壓大鼠差異不大。而高血壓大鼠的心率變異性變化與正常血壓大鼠比較，發現在光亮時的安靜睡眠其R-R間距較短，低頻對高頻比值較高，但高頻功率無顯著變化。有趣的是高血壓大鼠心率變異性各參數光亮光暗變化的斜率小於正常血壓大鼠，表示高血壓大鼠的心率變異性各參數全天性變異 (circadian variation) 比正常血壓大鼠來得小。當光照週期相位移延遲四小時，發現睡眠型態到第五天適應新節律，而R-R間距則在第四天適應新節律。本論文提供長時間觀察正常血壓大鼠及高血壓大鼠在不同光照週期其睡眠型態及相關自主神經活性之變化，可以了解更多訊息，未來可以進一步釐清高血壓之成因，或光照週期改變時自主神經所扮演角色之探討。

Many evidences had provided important links among circadian rhythm disorder and/or sleep disorder and essential hypertension. However, the interactions between circadian rhythm and sleep stages on cardiac autonomic functions remain unclear. This study was designed to investigate the autonomic differences of sleep stages between light and dark period in spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY), and whether there were any differences between SHR and WKY throughout a day. All WKY and SHR had electrodes implanted for polygraphic recordings. One week later, a 24-hour sleep-wakefulness recording session was analyzed. Twenty-four hours of electroencephalogram (EEG), electromyogram and electrocardiogram were recorded in freely moving rats throughout a 24-h diurnal cycle, consisting of a 12-h light and a 12-h dark period. Frequency-domain analysis of the stationary R-R intervals (RR) was performed 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) stages between light and dark periods of the day were compared. As compared with WKY, the accumulated time of SHR was longer at AW stage and shorter at QS stage in light period and the accumulated time of SHR was shorter at AW stage and longer at PS stage in dark period. The d-power percentage of EEG during QS stage was significantly lower in SHR in light period but was similar with WKY in dark period. Similar with WKY, the RR and TP during AW stage, and HF during each stage were significantly lower in the dark period than those in the light period in SHR. The HF in SHR was significantly lower than those in WKY during each stage and each period. The LF/HF during QS stage was significantly higher in SHR than those in WKY both the light and dark period. Shifting the light-dark cycle by 4 h resulted in immediate significant changes in sleep pattern and heart rate variability. There was a gradual shift in sleep pattern to a new rhythm that appeared to stabilize from shift day 5, and R-R interval values were shifted in a new rhythm by day 4. These results indicate that both rat strains had decreased cardiac vagal activity but increased sympathetic modulation during sleep in dark period than that in light period. SHR has a more interrupted sleep and elevated sympathetic activity both during light and dark periods as compared to WKY. These differences of sleep and related autonomic functions in SHR may play an important role in the developing of hypertension.

中文摘要 1
英文摘要 2
背景介紹 4
前言 4
睡眠相關自主神經功能研究之重要性 5
睡眠生理學 5
自主神經學 6
睡眠與自主神經功能 6
睡眠相關自主神經活性之日變週期變化 7
光線對日變週期的影響 7
日變週期與自主神經活性 7
日變週期與睡眠生理學 8
時差引起睡眠與循環系統之變化 8
高血壓合併睡眠與自主神經之日變週期變化 9
高血壓與自主神經學 9
高血壓與睡眠生理 10
高血壓與日變週期 11
心率變異性與心臟自主神經功能 11
目前長期研究睡眠相關自主神經功能之限制 13
研究動機與目的 15
研究動機 15
研究目的 15
重要性 16
材料與方法 17
實驗分組 17
動物處理 18
實驗流程 18
訊號收集 19
睡眠型式分析 19
腦波與肌電波之頻域分析 19
睡眠分期 20
睡眠腦波分析 20
心率變異性分析 20
心電訊號處理 20
心電訊號頻域分析 21
頻譜分析判讀 21
統計分析 21
實驗結果 22
光照週期對正常血壓大鼠睡醒型態及心臟自主神經功能之影響 22
正常血壓大鼠12小時光亮期與12小時光暗期睡醒型態之變化 22
正常血壓大鼠12小時光亮期與12小時光暗期睡醒各期心率變異性各參數之變化 23
光照週期對高血壓大鼠睡醒型態及心臟自主神經功能與正常血壓大鼠比較之特異表現 24
高血壓大鼠與正常血壓大鼠12小時光亮期與12小時光暗期睡醒型態變化之比較 24
正常光照週期高血壓大鼠與正常血壓大鼠於12小時光亮期及12小時光暗期睡醒各期心率變異性各參數之比較 25
光照週期改變對正常血壓大鼠睡醒型態及心臟自主神經功能之影響 26
綜合討論 27
本論文之最重要發現 27
光照週期對正常血壓大鼠睡醒型態及心臟自主神經功能之影響 27
正常血壓大鼠睡醒型態之變化 27
正常血壓大鼠心臟自主神經活性之變化 28
光照週期對高血壓大鼠睡醒型態及心臟自主神經功能與正常血壓大鼠比較之特異表現 29
高血壓大鼠睡醒型態之變化 29
高血壓大鼠心臟自主神經活性之變化 30
光照週期改變造成大鼠各生理現象調適情形之觀察 30
本論文之檢討 31
動物隻數 31
其他生理訊號 31
相位移時間長度選取及實驗天數 31
未來展望 32
結論 33
參考文獻 34

Akselrod S, Eliash S, Oz O, Cohen S (1987) Hemodynamic regulation in SHR: investigation by spectral analysis. Am J Physiol 253:H176-H183.
Akselrod S, Gordon D, Ubel FA, Shannon DC, Berger AC, Cohen RJ (1981) Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 213:220-222.
Bonnet MH, Arand DL (1998) Heart rate variability in insomniacs and matched normal sleepers. Psychosom Med 60:610-615.
Briaud SA, Zhang BL, Sannajust F (2004) Continuous light exposure and sympathectomy suppress circadian rhythm of blood pressure in rats. J Cardiovasc Pharmacol Ther 9:97-105.
Burgess HJ, Trinder J, Kim Y, Luke D (1997) Sleep and circadian influences on cardiac autonomic nervous system activity. Am J Physiol 273:1761-1768.
Chen HY, Kuo TBJ, Shaw FZ, Lai CJ, Yang CCH (2005) Sleep-related vagotonic effect of zolpidem in rats. Psychopharmacology (Berl) 181:270-279.
El-Mas MM, Abdel-Rahman AA (2005) Longitudinal studies on the effect of hypertension on circadian hemodynamic and autonomic rhythms in telemetered rats. Life Sci 76:901-915.
Franco P, Seret N, Van Hees JN, Lanquart JP, Groswasser J, Kahn A (2003) Cardiac changes during sleep in sleep-deprived infants. Sleep 26:845-848.
Goldstein DS (1983) Plasma catecholamines and essential hypertension. An analytical review. Hypertension 5:86-99.
Hashimoto M, Kuwahara M, Tsubone H, Sugano S (1999) Diurnal variation of autonomic nervous activity in the rat: investigation by power spectral analysis of heart rate variability. J Electrocardiol 32:167-171.
Julius S, Johnson EH (1985) Stress, autonomic hyperactivity and essential hypertension: an enigma. J Hypertens Suppl 3:S11-S17.
Kayama Y, Koyama Y (1998) Brainstem neural mechanisms of sleep and wakefulness. Eur Urol 33 Suppl 3:12-15.
Kuo TBJ, Lai CJ, Shaw FZ, Lai CW, Yang CCH (2004a) Sleep-related sympathovagal imbalance in SHR. Am J Physiol 286:H1170-H1176.
Kuo TBJ, Lin T, Yang CCH, Li CL, Chen CF, Chou P (1999) Effect of aging on gender differences in neural control of heart rate. Am J Physiol 277:H2233-H2239.
Kuo TBJ, Shaw FZ, Lai CJ, Lai CW, Yang CCH (2004b) Changes in sleep patterns in spontaneously hypertensive rats. Sleep 27:406-412.
Kuo TBJ, Yang CCH (2000) Altered frequency characteristic of central vasomotor control in SHR. Am J Physiol 278:201-207.
Kuo TBJ, Yang CCH (2004) Scatterplot analysis of EEG slow-wave magnitude and heart rate variability: an integrative exploration of cerebral cortical and autonomic functions. Sleep 27:648-656.
Kuo TBJ, Yang CCH (2005) Sleep-related changes in cardiovascular neural regulation in spontaneously hypertensive rats. Circulation 112:849-854.
MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, Abbott R, Godwin J, Dyer A, Stamler J (1990) Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 335:765-774.
Minami N, Imai Y, Munakata M, Sasaki S, Sekino H, Abe K, Yoshinaga K (1988) Reversed circadian rhythm of blood pressure in adult spontaneously hypertensive rats. J Hypertens Suppl 6:70-73.
Monti JM, Alvarino F, Monti D (2000) Conventional and power spectrum analysis of the effects of zolpidem on sleep EEG in patients with chronic primary insomnia. Sleep 23:1075-1084.
Muller JE, Tofler GH, Stone PH (1989) Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 79:733-743.
Murphy PJ, Campbell SS (1996) Physiology of the circadian system in animals and humans. J Clin Neurophysiol 13:2-16.
Peppard PE, Young T, Palta M, Skatrud J (2000) Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 342:1378-1384.
Refinetti R (1996) Comparison of the body temperature rhythms of diurnal and nocturnal rodents. J Exp Zool 275:67-70.
Salo TM, Jula AM, Piha JS, Kantola IM, Pelttari L, Rauhala E, Metsala TH, Jalonen JO, Voipio-Pulkki LM, Viikari JS (2000) Comparison of autonomic withdrawal in men with obstructive sleep apnea syndrome, systemic hypertension, and neither condition. Am J Cardiol 85:232-238.
Schwartz PJ, La Rovere MT, Vanoli E (1992) Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. Circulation 85:I77-191.
Schwartz S, McDowell Anderson W, Cole SR, Cornoni-Huntley J, Hays JC, Blazer D (1999) Insomnia and heart disease: a review of epidemiologic studies. J Psychosom Res 47:313-333.
Shaw FZ, Lai CJ, Chiu TH (2002) A low-noise flexible integrated system for recording and analysis of multiple electrical signals during sleep-wake states in rats. J Neurosci Methods 118:77-87.
Somers VK, Dyken ME, Mark AL, Abboud FM (1993) Sympathetic-nerve activity during sleep in normal subjects. N Engl J Med 328:303-307.
Suka M, Yoshida K, Sugimori H (2003) Persistent insomnia is a predictor of hypertension in Japanese male workers. J Occup Health 45:344-350.
Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996) Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation 93:1043-1065.
Trinder J, Kleiman J, Carrington M, Smith S, Breen S, Tan N, Kim Y (2001) Autonomic activity during human sleep as a function of time and sleep stage. J Sleep Res 10:253-264.
Tucker DC, Domino JV (1988) Balance among autonomic controls of heart rate in neonatal spontaneously hypertensive and borderline hypertensive rats. J Auton Nerv Syst 22:11-21.
Vilaplana J, Madrid JA, Sanchez-Vazquez J, Campuzano A, Cambras T, Diez-Noguera A (1995) Influence of period length of light/dark cycles on the body weight and food intake of young rats. Physiol Behav 58:9-13.
Willich SN, Levy D, Rocco MB, Tofler GH, Stone PH, Muller JE (1987) Circadian variation in the incidence of sudden cardiac death in the framingham heart study population. Am J Cardiol 60:801-806.
Wolf MM, Varigos GA, Hunt D, Sloman JG (1978) Sinus arrhythmia in acute myocardial infarction. Med J Aust 2:52-53.
Yang CCH, Kuo TBJ (1999) Assessment of cardiac sympathetic regulation by respiratory-related arterial pressure variability in the rat. J Physiol 515:887-896.
Yang CCH, Kuo TBJ, Chan SHH (1996) Auto- and cross-spectral analysis of cardiovascular fluctuations during pentobarbital anesthesia in the rat. Am J Physiol 270:575-582.
Yang CCH, Lai CW, Lai HY, Kuo TBJ (2002) Relationship between electroencephalogram slow-wave magnitude and heart rate variability during sleep in humans. Neuroscience Letters 329:213-216.
Yang CCH, Shaw FZ, Lai CJ, Lai CW, Kuo TBJ (2003) Relationship between electroencephalogram slow-wave magnitude and heart rate variability during sleep in rats. Neuroscience Letters 336:21-24.