臺灣博碩士論文加值系統

背景：
腦血管疾病已位居國人十大死因的第二位，會造成個體的死亡和殘疾。中風好
發的位置位於中大腦動脈，它位在腦內威廉氏環附近。中大腦動脈阻塞(MCAO)
與高血壓的個體有密切相關並會造成個體的睡眠障礙甚至造成腦部缺血性中風
的嚴重度。而MCAO 的動物模式在模擬中風之研究已延用多年，也多所探討
MCAO 對腦波、睡眠、自主神經的影響，但學者大多使用麻醉情況下進行生理
功能探討，較少在自由活動下，長時間瞭解這些生理參數的變化。然而自由活動
大鼠具睡醒的頻繁切換，特別對於對於睡眠當中自主神經功能的變化不甚明瞭。
因此本論文的研究主要是瞭解MCAO 前後對自由活動下大鼠的腦波、睡眠和自
主神經的影響，特別是高血壓和正常血壓的差異。
目標：
1. TTC 染色探討Wister-Kyoto rats (WKY) 和spontaneously hypertensive rats
(SHR)在MCAO 後，其腦部受損區域之體積之差異。
2. WKY 和SHR 在MCAO 前後對腦部活性的變化(中風側和健側之比較)。
3. WKY 和SHR 在MCAO 前後對睡眠結構之變化。
4. WKY 和SHR 在MCAO 前後心臟自主神經功能的變化。
方法：
將八週大同年齡的WKY 和SHR 埋置頭電極，之後隨機區挑選做MCAO 和Sham
III
手術，術後每週測一次持續4 週。一個月後，犧牲取腦做切片染色。
結果：
從TTC 染色可以看出中風後SHR 的腦部受損的範圍較中風後WKY 嚴重，相對的
在腦波的部份也可看出SHR 在右側頂葉和右側額葉的腦波功率(TP, delta power,
theta power, alpha power, beta power)較WKY 低。然而中風後的WKY 則較無太大
改變。
在睡眠上，控制組之SHR 本身在睡眠時間較WKY 短，睡眠品質差。但MCAO 對
WKY 和SHR 的睡眠結構並無太大改變。
MCAO 對WKY 和SHR 皆會造成心率變異性的TP, HF, LF 的降低，但是WKY 影
響的是長期的改變，而SHR 在中風後第15 天即會回升至MCAO 前的狀況。但SHR
在MCAO 後LF/HF 其皆明顯比MCAO 前及MCAO 之WKY 低。
結論：
MCAO 造成正常血壓和高血壓的生理影響不一，可能是SHR 體內缺乏血管保護因
子，因此造成其腦部皮質受損的範圍較WKY 大，相對的從腦波也可看出SHR 的受
傷側的腦波活性亦較低。然而MCAO 對自主神經影響的方面，WKY 較嚴重，最主
要是在副交感神經的部份。但SHR 在MCAO 則主要是降低交感神經。

Background：
Stroke now ranks second as leading cause of death which makes death and
long-term disability. The occlusion of the middle cerebral artery (MCAO) which
nears the circle of Willis almost results in a large cerebral infarct in adult rats. With
a close relationship of hypertension, MCAO not only causes sleep disorders but
also affects the severity of ischemic stroke. Being an animal model of stroke
research for many years, MCAO explores the influence on EEG, sleep and
autonomic nerve system. However, most researchers focus on the physiological
under anesthesia than the change of physiological index in free moving rats. It is
still unclear that the change of ANS in free moving rats. Therefore, the aim of this
study is to explore the influence of EEG, sleep, ANS in before and after MCAO,
especially the difference between hypertension and normal blood pressure.
Aims：
1. To study the difference of the capacity of brain before and after MCAO in WKY
and SHR by TTC stain.
2. To study the changes of brain activity before and after MCAO in WKY and SHR.
3. To study the changes of sleep pattern before and after MCAO in WKY and SHR.
4. To study the changes of cardiac autonomic nervous system before and after
MCAO in WKY and SHR.
Methods：
The MCAO was injured focal cerebral ischemia which followed in adult male WKY
and compared with age-matched SHR. Six hours of electroencephalogram (EEG),
electromyogram (EMG) and electrocardiogram (ECG) signals were recorded in
V
rats during daytim. Rats were sacrificed one month after MCA occlusion and
administration of 2,3,5-triphenylterazolium chloride.
Results：
Comparing with WKY, SHR showed an increase in infarct volume following MCAO.
The MCAO effect of EEG at R-Parietal and frontal of SHR showed decrease in
total power (TP), delta power, theta power, alpha power and beta power . However,
WKY were not changes.
As compared to WKY, SHR may have less sleep time, poorer sleep quality in Sham
groups. However, MCAO and Sham groups had similar sleep pattern in sleep time,
stage number and stage duration.
A significant decrease in TP, high-frequency power (HF) and low-frequency power
(LF) of heart rate variability in active waking (AW), quiet sleep (QS), and
paradoxical sleep (PS) stages was found in MCAO group in both SHR and WKY
rats. WKY returned to baseline in the long time. As compared WKY, SHR
decreased LF/HF ratio in AW, QS and PS stages.
Conclusions：
SHR lacks the natural proneness to stroke, but WKY were protected from infarction.
But WKY had decreased and prolonged cardiac parasympathetic tone. SHR had
attenuate cardiac sympathetic tone. In this study, we suggest that the cardiac
autonomic regulation of SHR and WKY were different to stroke, it may be
accommodation circulation in the occlusion. However, comparing with WKY rats,
SHR rats had serious cerebral cortex damage.

致謝…………………………………………………………………………I
中文摘要…………………………………………………………………·II
英文摘要…………………………………………………………………·IV
目錄………………………………………………………………………··VI
背景介紹……………………………………………………………………1
前言…………………………………………………………………………1
腦中風………………………………………………………………………2
腦中風在動物模式的應用…………………………………………………3
腦波…………………………………………………………………………4
腦中風的腦波及睡眠………………………………………………………5
腦中風對自主神經功能的影響……………………………………………6
睡眠生理與神經活性的關聯………………………………………………8
腦中風與高血壓的關係……………………………………………………9
心率變異與心臟自主神經功能…………………………………………·10
研究動機…………………………………………………………………·14
研究目的…………………………………………………………………·15
材料與方法………………………………………………………………·16
實驗動物…………………………………………………………………·16
VII
實驗分組…………………………………………………………………·16
實驗步驟…………………………………………………………………·16
頭電極埋置………………………………………………………………·16
中大腦動脈手術…………………………………………………………·17
2,3,5-triphenyltetrazolium chloride (TTC) 染色……………………··18
訊號收集與分析方式……………………………………………………·18
訊號的收集………………………………………………………………·18
腦波與肌電之頻域分析…………………………………………………·19
心電訊號處理……………………………………………………………·19
心電訊號頻域分析………………………………………………………·20
心率變異性的判讀………………………………………………………·21
睡眠判讀…………………………………………………………………·21
統計分析…………………………………………………………………·22
實驗結果…………………………………………………………………·23
一、TTC 染色探討WKY 和SHR 在MCAO 後其腦部受損區域之體積差
異……………………………………………………………·……···23
二、WKY 和SHR 在MCAO 前後對腦部活性的變化(中風側和健側之比
較) ……………………………………………………………·……·23
三、WKY 和SHR 在MCAO 前後對睡眠結構之變化…………………·……24
VIII
四、WKY 和SHR 在MCAO 前後對心臟自主神經功能的變
化……………………………………………………………………·25
綜合討論…………………………………………………………………·28
腦波………………………………………………………………………·28
睡眠………………………………………………………………………·29
自主神經…………………………………………………………………·30
本論文之檢討……………………………………………………………·32
長期記錄的訊號品質維持………………………………………………·32
對整個24 小時睡眠尚不清楚……………………………………………32
尚未釐清造成高血壓大鼠和正常血壓大鼠中風後現象表現的真正原
因…………………………………………………………………………·32
未來展望…………………………………………………………………·33
結論………………………………………………………………………··34
附表、圖…………………………………………………………………·35
參考文獻…………………………………………………………………·60

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