長期暴露於間歇性低氧，如同阻塞型睡眠呼吸中止症病患於睡眠期間處於反覆性呼吸中止現象，可導致系統性高血壓。臨床上更發現高血壓患者亦具有較高比率罹患阻塞型睡眠呼吸中止症。間歇性低氧就如同缺氧再獲氧的情況下，會使細胞內產生大量的反應性氧衍生物。本實驗欲比較自發性高血壓大鼠 (SHR)、Wistar-Kyoto (WKY)品系之正常血壓大鼠和 Sprague-Dawley rats (SD)大鼠於間歇性低氧情況下，其動脈化學反射、心臟交感神經調節以及平均動脈血壓上是否有所差異。並且去確認反應性氧衍生物是否參與這些心肺功能之反應的變化。本實驗採用八至九週大之成熟雄性大鼠，每天於動物光亮期 (10 AM – 4 AM)暴露於間歇性低氧或正常空氣環境之周期為75秒/次 (灌流30秒的氮氣後，再予灌流45秒的空氣)的間歇性低氧，每天持續六小時，連續觀察三十天。使用非侵入性無線遙測儀系統偵測每天動脈血壓訊號，並將此動脈血壓訊號再經由平均動脈血壓以及心率變異性分析，用以評估自主神經功能之活性。每天測量清醒動物於空氣及急性低氧 (12% O2)下，其大鼠呼吸速率、潮氣容積、每分鐘肺通氣量等化學反射之指標。實驗結果發現到在間歇性低氧或空氣之暴露下WKY和SD的平均動脈血壓是相類似的，且皆都顯著較SHR低。與WKY及SD相比，SHR在間歇性低氧或空氣暴露後，交感神經血管運動調控指標之反應有明顯上升。而比較三種品系大鼠，間歇性低氧並未造成在心跳速率以及心臟副交感神經活性指標反應之變化，但在心臟交感神經活性指標反應上升之變化類似。此外，間歇性低氧在三種品系大鼠上，引起每分鐘通氣量 (動脈化學反射活性的指標)及孤獨核尾部FosB之表現量是相類似的。而先前以腹腔注射給予N-acetylcysteine (一種抗氧化劑，250 mg/kg) 能預防間歇性低氧下提高之心肺反應及孤獨核尾部FosB的表現量。根據上述結果可間接推測，1) 此三種品系大鼠，間歇性低氧引發之高血壓可能與動脈化學反射活化及交感神經活性增加有關。2) ROS可能參與間歇性低氧所引發的這些心肺反應。

Long-term exposure to intermittent hypoxia (IH), such as that which occurs with obstructive sleep apnea (OSA), may be one factor contributing to systemic hypertension seen in OSA patients. Importantly, OSA occurs frequently in the hypertensive patients. IH seems to resemble hypoxia-reoxygenation, wherein cellular generation of reactive oxygen species (ROS). The present study attempted to evaluate the differences in arterial chemoreflex, cardiac autonomic modulations, and mean arterial pressure (MAP) among spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD) following IH exposure, and to determine the role of ROS involves in eliciting these cardiopulmonary alternations in these conscious unrestrained rats. We used age-matched (8-9-wk-old) adult male rats exposed to repetitive 1.25-min cycles (30 s of N2 + 45 s of 21% O2) of IH or room air (RA) for 6 h/day during light phase (10 AM-4 PM) for 30 days. Blood pressure signals were measured daily by the telemetry system, which were used to assess the autonomic function by MAP and heart rate variability analysis. Respiratory responses during RA breathing and acute hypoxia (12% O2), the indices for tonic and phasic chemoreflex activation, respectively, were measured daily using the barometric technique of plethysmography. WKY and SD had similar MAP, which is significantly lower than that of SHR after RA or IH exposure. Furthermore, SHR developed higher low-frequency power of the MAP spectrogram (BLF) (an index for sympathetic vasomotor activity) after RA or IH exposure. Among three strains of rats, IH did not induce changes in high-frequency power of pulses interval spectrogram (HF) (an index for cardiac vagal activity) and heart rate, but a similar increase in normalized low-frequency power of pulses interval spectrogram (LF%) (an index for cardiac sympathetic outflow). Additionally, IH challenge exhibited a similar and significant increase in minute ventilation (an index for arterial chemoreflex activation) and FosB expression in caudal nucleus tractus solitarius (cNTS) in three strains of rats. Intraperitoneal injection of N-acetylcysteine (an antioxidant, 250 mg/kg, i.p.) totally prevented IH-induced the elevations of the cardiorespiratory responses and FosB expression in cNTS. These results suggest that 1) IH-induced hypertension may be associated with arterial chemoreflex activation and facilitation of sympathetic outflow in three different strains of rats; and 2) ROS may involve in IH-induced these cardiorespiratory responses.

目錄 I
中文摘要 III
英文摘要 V
壹、緒言 1
重要性 1
背景知識 1
一、 長期間歇性低氧對生理之影響 3
二、長期間歇性低氧引發週邊動脈化學反射反應之變化 3
三、間歇性低氧對自主神經功能之影響 5
四、反應性氧衍生物參與於長期間歇性低氧中之變化 6
五、反應性氧衍生物參與於長期間歇性低氧所引發心血管反應過程之可能性 8
六、高血壓導致睡眠呼吸中止增加之可能原因 9
七、研究目的 10
貳、實驗材料與方法 11
一、實驗動物 11
二、血壓訊號無線遙測器之埋設手術 11
三、間歇性低氧模式 12
四、正常氧分壓模式 12
五、血壓之測量 12
六、自主神經功能之分析 13
七、動脈化學反射反應之測量 14
八、動物犧牲與組織處理 15
九、免疫組織化學染色 15
十、藥品 16
十一、實驗設計及步驟 16
十二、統計分析 19
参、實驗結果 20
一、長期間歇性低氧暴露對大鼠其動脈化學反射反應之影響 20
二、長期間歇性低氧暴露對大鼠其心血管反應之影響 24
三、長期間歇性低氧暴露對大鼠孤獨核尾部之影響 31
肆、討論 32
伍、圖表與說明 40
陸、參考文獻 110

陸、參考文獻

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