利用去卵巢大鼠探討雌激素對腦部二十二碳六烯酸含量之影響

Effect of estrogen on brain docosahexaenoic acid levels studied in ovariectomized rats

何宸怡(Chen-I Ho)

指導教授 ： 蘇慧敏

國立臺灣大學/醫學院/生理學研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.10188

摘要

二十二碳六烯酸 (docosahexaenoic acid，DHA，22:6n-3) 富含於腦部神經細胞膜，為影響腦部神經發育生長與維持功能的重要因子。雌激素除了生殖功能之外，也會影響情緒及認知功能。停經後婦女，血漿雌激素和DHA含量皆有下降之情形，得到阿茲海默氏症的機率也比同年紀的男性高。臨床研究發現停經後婦女接受雌激素補充療法後，血漿中的 DHA 濃度會顯著高於未進行雌激素補充療法之停經後婦女。針對變性人之研究也發現，女變男之變性人，接受卵巢摘除手術和睪固酮之後，其血漿DHA含量會下降。阿茲海默氏症患者腦部DHA含量有下降的現象，而婦女停經後血漿DHA含量下降，但其腦部DHA含量是否會受影響還不得而知。因此本研究主要探討雌激素能否影響各腦區之DHA 的含量，進而釐清雌激素與 DHA 之間的關聯性。

在飲食 n-3 脂肪酸充足情況下，以去卵巢剝奪9個月齡Spraque-Dawley大鼠體內雌激素，並於12個月大犧牲，以其組織進行脂肪酸分析，結果發現僅在紅血球、肝臟及下視丘有DHA含量下降之情形，而額外給予魚油補充對大鼠組織DHA含量沒有影響。

在飲食n-3脂肪酸缺乏情況下，以去卵巢剝奪2個月齡SD大鼠其體內雌激素，並在七個月大時開始給予魚油和/或雌激素以及安慰劑至大鼠12個月大時進行犧牲，收集腦部及紅血球、肝臟組織，進行脂肪酸分析。結果發現終生餵飼 n-3脂肪酸缺乏飼糧之大鼠，卵巢切除後其肝臟、紅血球、下視丘、嗅球及海馬迴之DHA含量顯著低於假手術之大鼠，而給予魚油補充能顯著增加去卵巢大鼠組織之DHA含量。除此之外，同時給予雌二醇及魚油補充大鼠，其肝臟和下視丘之DHA含量會顯著上升。由此結果可得知，以卵巢摘除剝奪雌激素，會使大鼠腦部DHA含量下降。

綜合本研究2個實驗可知，終生食用chow diet 之12個月齡大鼠，去卵巢三個月會使其紅血球、肝臟、下視丘之DHA含量顯著下降，而終生食用n-3 deficient diet 之12個月齡大鼠，去卵巢10個月會使其肝臟、紅血球、下視丘、嗅球及海馬迴之DHA含量顯著下降。

關鍵字

雌激素 ； 二十二碳六烯酸 ； 去卵巢大鼠

並列摘要

Docosahexaenoic acid (DHA, 22:6n-3) is mainly enriched in neuronal membrane and is essential for normal neurological function. Postmenopausal women with estrogen replacement therapy have higher plasma DHA levels than those without therapy. Plasma DHA levels are decreased in female-to-male transsexual subjects who have undergone ovariectomy and are receiving testosterone. But there is still no direct evidence shown in brain for this finding. Female rats exposed to a n-3 fatty acids deficient diet during perinatal period from embryo to weaning at postnatal day 21 via maternal intake, and the offspring were maintained on this n-3fatty acid-deficient diet through their life. At 2-month-old, the rats were subjected to bilateral ovariectomy (OVX) or sham operation (sham). At 7-month-old, the rats received either fish oil, estradiol or both estradiol and fish oil daily till scarified at 12-month-old. We found that the DHA levels were significantly reduced in hippocampus, hypothalamus and olfactory bulbs in the OVX rats compared to the sham rats. The DHA levels were significantly higher in liver, RBC, hypothalamus, hippocampus, cortex and olfactory bulb in the OVX rats supplemented with fish oil. In addition, DHA levels were significantly increased in hypothalamus and liver in the OVX rats supplemented with both fish and estradiol compared to the rats supplemented with fish oil only. It was concluded that estrogen deprivation by OVX did reduce brain DHA levels.

並列關鍵字

estrogen ； DHA ； Ovx rats

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