臺灣博碩士論文加值系統

長期間歇性低氧，如同發生睡眠呼吸中止之狀態，可導致許多心血管疾病之發生。然而，持續性高血壓的原因可能是由於長期間歇性低氧的反覆刺激頸動脈體，促使交感神經持續興奮所導致。本實驗室先前的數據顯示，再給予長期間歇性低氧暴露之卵巢切除雌鼠，其心肺反應有明顯增加的趨勢。因此我們推測內生性荷爾蒙，尤其是雌激素對於雌性大鼠有預防因長期間歇性低氧所引發之高血壓症狀。故本實驗欲探討清醒之卵巢切除雌鼠皮下給予雌二醇(150 微克/公斤/天)或是植物性大豆異黃酮(5 毫克/公斤/天)並且連續暴露25天長期間歇性低氧，觀察其心肺反應是否有增強？實驗中給予間歇性低氧與一般空氣的條件為(30秒氮氣 + 45秒空氣)一次循環為75秒，每日於光照期暴露6小時，連續25天。而實驗結果發現注射溶劑之的卵巢切除雌鼠，於長期間歇性低氧的刺激下，造成動脈化學反射反應提高，交感神經興奮與平均動脈血壓升高。然而，若事先給予卵巢切除雌鼠補充雌二醇之後，則會抑制因長期間歇性低氧所提高上述之心肺反應。此外，大豆異黃酮的補充亦可明顯降低因長期間歇性低氧，活化動脈化學反射反應，提高之交感神經活性與平均動脈血壓。相反地，此雌二醇與大豆異黃酮的保護作用可被ICI-182780(非特異性雌激素受體拮抗劑)完全阻斷。另外，此雌二醇與大豆異黃酮皆在空氣組能明顯地改變控制組雌鼠之心肺反應。根據研究結果可推測，給予卵巢切除雌鼠額外補充雌二醇或大豆異黃酮，可藉由雌激素受體而抑制因長期間歇性低氧所提高之心肺反應。

Chronic intermittent hypoxia (CIH), such as that occurring in association with obstructive sleep apnea (OSA), may be one factor leading to hypertension in OSA. Nevertheless, the development of sustained hypertension may be attributed to an increased sympathetic outflow due to the repeated carotid body stimulation under CIH. Our laboratory previously reported that CIH-exposed ovariectomized (OVX) female rats, but not in intact female rats, exhibited significant increases in the cardiorespiratory parameters during the observation period. Accordingly, we hypothesized that circulating sex hormone, in particular, estrogen in female rats will protect against the CIH-induced hypertension. This study investigated whether these elevated cardiorespiratory responses in CIH-exposed OVX female rats can be improved by subcutaneous administration with 17β-estradiol (150 μg/kg/day) or phytoestrogen genistein (a soy derived isoflavone; 5 mg/kg/day). Adult female Sprague-Dawley rats were exposed to repetitive 75-sec cycles (30s of N2 + 45 s of 21% O2) of intermittent hypoxia or room air (RA) for 6 h/day during light phase for 25 days. In vehicle-treated OVX rats, CIH-induced elevated mean arterial pressure (MAP), low-frequency power of MAP (BLF; an index for sympathetic vasomotor activity), normalized low-frequency power of interpulse interval (LF%; an index for cardiac sympathetic outflow), and arterial chemoreflex activation. Treatment of OVX rats with 17β-estradiol abolished these elevated cardiorespiratory responses by CIH. Furthermore, genistein supplementation also markedly attenuated these elevated MAP, BLF, LF%, and arterial chemoreflex activation in CIH-exposed OVX rats. In contrast, the protective effect of 17β-estradiol and genistein was completely blocked by administration of ICI-182780 (a nonspecific estrogen receptor antagonist). None of these pretreatments significantly affected these cardiorespiratory parameters during the observation period in RA group. These results suggest that exogenous supplementation of 17β-estradiol or phytoestrogen genistein prevents these elevated cardiorespiratory responses in CIH-exposed OVX rats, and this protective effect is mediated through the action of estrogen receptor.

目錄
中文摘要 IIII
英文摘要 VI
壹、緒言 1
貳、實驗材料與方法 11
参、實驗結果 20
肆、討論 30
伍、圖表與說明 35
陸、參考文獻 74

陸、參考文獻

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