n-3多元不飽和脂肪酸對老化合併代謝症候群大鼠其認知功能及憂鬱症狀之影響

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題名:	n-3多元不飽和脂肪酸對老化合併代謝症候群大鼠其認知功能及憂鬱症狀之影響 Effects of n-3 Polyunsaturated Fatty Acids on Cognitive Impairments and Depressive Behaviour in Aged Rats with Metabolic Syndrome
作者:	郭育儒 Guo, Yu-Ru
貢獻者:	黃士懿
關鍵詞:	老化;代謝症候群;n-3多元不飽和脂肪酸;認知功能損傷;憂鬱症 ageing;metabolic syndrome;n-3 polyunsaturated fatty acids;cognitive impairment;depression
日期:	2016-12-06
上傳時間:	2020-09-23 10:15:05 (UTC+8)
摘要:	老化現象與其衍生的疾病是大部分國家面臨的重大醫療挑戰之一，其影響又以老年發生率較高的認知功能損傷及憂鬱症等精神疾病為主，而代謝症候群被列為與老年精神疾病相關，其伴隨而來的種種疾病亦造成社會極大負擔。流行病學研究指出老年人飲食中若缺乏攝取n-3多元不飽和脂肪酸(n-3 PUFA)與認知功能損傷和憂鬱症病發密切相關，而n-3 PUFA已被大量臨床及動物研究證實其抗發炎的正面效應，但其在老化過程中所扮演的角色則尚未釐清。本論文於實驗一探討n-3 PUFA對於自然老化合併代謝症候群大鼠的認知功能及憂鬱症狀影響。實驗設計為飼養大鼠至102周齡後於飲水中添加35 %蔗糖持續6周，再於飲食中介入魚油或亞麻籽油，待8週後利用水迷宮試驗和強迫游水試驗測試大鼠的認知功能及類似憂鬱症狀的情形。研究結果顯示n-3 PUFA可能透過降低血糖、體脂和血脂等代謝症候群相關因子及增加腦部神經生長因子濃度與降低血漿中發炎反應，以達到減緩因自然老化和代謝症候群引發的認知功能損傷和憂鬱症狀的惡化。由於飼養老化大鼠耗時過久，研究指出長期給予大鼠D-半乳糖或許可以模擬自然老化且加速認知功能惡化的作用，故本論文於第二部分實驗運用D-半乳糖和高蔗糖飲食誘發大鼠產生老化合併代謝症候群，並於飲食中介入n-3 PUFA進行探討。本次實驗結果發現n-3 PUFA可透過減少TNF-α、RAGE和GFAP的表現來改善因為D-gal誘發老化產生的認知功能障礙；但無法改善對於D-gal誘發老化合併高蔗糖飲食引發的類似憂鬱症情境。本論文亦在最後一部分探討並比較大鼠自然老化與D-galactose誘發老化之異同，且於研究中提及的多項重要血液生化指標，有助於大鼠認知功能和憂鬱症情境的評估。 Ageing is one of the most important challenges that many countries and societies face. Psychiatric disorders in the elderly, mainly cognitive impairment and depression carry a heavy load of comorbidities such as metabolic syndrome. Epidemiological studies have reported that nutritional deficit of n-3 polyunsaturated fatty acids (n-3 PUFA) is closely related to cognitive impairment and depression in later life. The effects of n-3 PUFA on inflammation in human subjects have been extensively studied from both clinical and molecular point of view. However, the role of the ageing process as confounder in this relationship has not been consistently elucidated. Thus, we conducted a series of n-3 PUFA on ageing animal model. The first study was designed to investigate the effects of n-3 PUFA-rich oils on the behavioural impairment of unchallenged aged rats with metabolic syndrome by using a Morris water maze (MWM) test and forced swimming test (FST). Twenty 102-wk-old male SD male rats received a 35% sucrose solution and were fed with fish oil- or flaxseed oil-contained diets for 8 wk. The n-3 PUFAs treatments demonstrated significantly quicker MWM acquisition, shorter FST immobility time and higher levels of nerve growth factor than did the control group. Furthermore, n-3 PUFA-rich oil diets present the protective effects by improving fasting blood sugar levels and reducing proinflammatory cytokine levels, thus preventing cognitive age-related impairments and depressive-like behaviour in unchallenged aged prediabetic rats. Chronic systemic exposure of rodents to D-gal induces accelerated deterioration of cognitive and mental disease that similar to symptoms in natural aging. In the second study, we evaluated the effect of n-3 PUFA on spatial memory and depressive behavior in the D-galactose (D-gal)- and sucrose-induced aged rat with metabolic syndrome. Rats were co-treated with D-gal and sucrose solution and fed with fish oil- or flaxseed oil-contained diets for 8 weeks. The results showed cognitive impairment in the MWM after D-gal administration but not in n-3 PUFAs treated groups. Data showed that rats treated with D-gal and/or high-sucrose exhibited depressive behaviors than the normal group as well as in n-3 PUFAs treated groups in FST challenge. Besides, n-3 PUFA-rich diets reduced the levels of tumor necrosis factor α, receptor of advanced glycation end-products and glial fibrillary acidic protein in selected brain tissue. These results indicated that n-3 PUFA attenuating D-gal-inducing cognitive impairment but not depressive like behaviors. We also compared the differences between unchallenged and D-gal induced ageing rat combined high sucrose diet model in the last part. This study provides important biochemical index for evaluate cognitive and depressive status. In conclusion, our data provide evidence that n-3 PUFA rich oil can produce protective effects on cognitive impairments both in natural aged rats and D-gal induced ageing rat with metabolic syndrome. And n-3 PUFA rich oil prevented depressive-like behaviour in natural aged rats with metabolic syndrome, but failed in D-gal induced ageing rat.
描述:	博士指導教授:黃士懿委員:葉松鈴委員:謝榮鴻委員:王銘富委員:黃啟彰
資料類型:	thesis
顯示於類別:	[保健營養學系暨研究所] 博碩士論文

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