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| 題名: | 大豆蛋白對酒精性肝臟疾病大鼠酒精戒斷後的影響
Effects of Soy Protein on Alcoholic Liver Disease in Ethanol-Withdrawal Rats |
| 作者: | 保健營養學研究所 |
| 貢獻者: | 林筱珊
Lin Hsiao-Shan
陳俊榮 |
| 關鍵詞: | 碩士
指導教授-陳俊榮
委員-王銘富
委員-葉松鈴
酒精性肝臟疾病;大豆蛋白;酒精
alcoholic liver disease;soy protein;alcohol |
| 日期: | 2010 |
| 上傳時間: | 2010-10-20 12:36:39 (UTC+8) |
| 摘要: | 酒精性肝臟疾病是由於長時間大量飲酒所造成的。酒精代謝會產生許多自由基，造成氧化壓力上升，並使體內脂質代謝失去平衡，導致肝臟脂質堆積；另外，也會引起發炎反應，進一步促進肝臟組織損傷。本研究目的在於探討誘發實驗動物酒精性肝臟疾病後，酒精戒斷並給予大豆蛋白介入是否可改善酒精造成肝臟脂質堆積、氧化壓力及發炎反應增加的情形。將實驗動物分為控制組 (C) 和酒精組 (E)，進入為期 12 週的酒精性肝臟疾病誘發期，之後再將酒精組分為酒精戒斷組 (EC) 和酒精戒斷大豆蛋白組 (EP)，進入為期 4 週之大豆蛋白介入實驗期。酒精性肝臟疾病誘發期使用控制組液態飼料和低醣酒精液態飼料配方，皆為等熱量液態飼料，酒精提供 34.5% 熱量，控制組則以麥芽糊精取代酒精提供之熱量，且以 pair-feed 方式餵食。大豆蛋白介入實驗期皆給予控制組液態飼料，其中大豆蛋白組以大豆蛋白全量取代控制組液態飼料之酪蛋白。酒精性肝臟疾病誘發期每隔 4 週採血一次進行血液分析，大豆蛋白介入實驗期第 0、2 及 4 週犧牲部分實驗動物，收集血液、肝臟進行分析。本次實驗結果發現：酒精組酒精攝取量為 11.4 g/kg/day，每日平均攝食量各組間並無顯著差異。酒精組在酒精性肝臟疾病誘發期結束後，肝臟有顯著的脂肪空泡堆積和發炎現象。而酒精戒斷並給予大豆蛋白介入，可顯著改善酒精造成的肝臟脂質代謝異常、降低脂質過氧化物、促發炎反應細胞激素、羥基脯胺酸濃度及骨髓過氧化酶酵素活性。此外，大豆蛋白介入也可以顯著降低酒精造成肝臟 CYP2E1 蛋白質表現量增加的情形，同時可以顯著增加酒精造成 PPAR-alpha 和 CYP4A 蛋白質表現量下降的情形。由肝臟病理切片結果：大豆蛋白可改善酒精造成肝臟脂肪空泡堆積和發炎細胞浸潤的現象。綜合以上結果得知：酒精性肝臟疾病動物模式中，酒精戒斷並給予大豆蛋白介入，可能經由降低促發炎反應細胞激素和 CYP2E1 蛋白質表現量及增加 PPAR-alpha 和 CYP4A 蛋白質表現量，進而改善酒精造成的肝臟脂質堆積、氧化壓力和發炎反應增加的情形，且酒精戒斷並給予大豆蛋白介入比單純酒精戒斷的效果佳。
Alcoholic liver disease (ALD) is the common consequence of prolong alcohol intake. The metabolism of alcohol generates free radicals which lead to increase oxidative stress, abnormal lipid metabolism, hepatic fat accumulation, and may further cause liver inflammation. The aim of this study is to investigate the effects of soy protein consumption on alcoholic liver disease (ALD). Rats were induced to have ALD with low carbohydrate ethanol liquid diet for 12 weeks and divided into the control group and two experiment groups: the EC group (control liquid diet) and the EP group (control liquid diet + soy protein) for 4 weeks. Diets of the experiment groups contain soy protein as substitution of all of casein. The control group was feed control liquid diet for 16 weeks. After soy protein intervention, we sacrificed partial rats at the 0, 2 and 4 week. Results showed that ethanol group could significantly increase hepatic lipid accumulation and inflammation, and that diet containing soy protein isolate could significantly decrease hepatic lipid, malondialdehyde, pro-inflammatory cytokines, hydroxyproline levels, and myeloperoxidase activity. Additionally, soy protein isolate intake lowered hepatic CYP2E1 protein expression, and increased hepatic PPAR-alpha and CYP4A protein expression. In conclusion, soy protein isolate may improve the alcohol-induced lipid accumulation, oxidative stress, and inflammation by decreasing pro-inflammatory cytokines and CYP2E1 protein expression, and increasing PPAR-alpha and CYP4A protein expression and thereby improve alcoholic liver disease progression. |
| 關聯: | 102頁 |
| 描述: | 摘要 I
ABSTRACT II
致謝 III
目錄 V
表目錄 VII
圖目錄 VIII
前言 1
第一章 研究動機與目的 4
第一節 酒精性肝臟疾病致病機制 4
第二節 大豆蛋白簡介 9
第三節 大豆蛋白與脂質代謝 10
第四節 大豆蛋白與氧化壓力 11
第五節 大豆蛋白與發炎反應 12
第六節 酒精性肝臟疾病實驗研究目的 13
第二章 材料與方法 15
一、實驗動物 15
二、液態飼料製備和餵食 15
三、實驗設計 16
四、樣品收集 17
五、分析項目 20
六、統計方法 37
第三章 結果 38
一、酒精性肝臟疾病動物誘發 38
二、酒精攝取量、攝食量、體重與攝食效率 39
三、血液生化分析 40
四、肝臟重量、肝重體重比值及肝臟脂質濃度分析 43
五、肝臟 PPAR?? 與 CYP4A 蛋白質表現量 45
六、糞便生化分析 46
七、脂肪組織 47
八、肝臟脂質過氧化產物濃度與抗氧化酵素活性 47
九、肝臟 CYP2E1 蛋白質表現量 48
十、肝臟 TNF-?恁BIL-1?? 及 IL-6 濃度 49
十一、肝臟 MYELOPEROXIDASE 與 HYDROXYPROLINE 濃度 50
十二、肝臟病理組織切片分析 51
第四章 討論 52
一、酒精性肝臟疾病動物模式之誘發 52
二、大豆蛋白對於實驗動物生長與營養狀態的影響 53
三、大豆蛋白對於酒精所造成之肝功能指數上升的影響 53
四、大豆蛋白對於因酒精所造成之肝臟脂質堆積的影響 54
1、酒精對肝臟脂質堆積之影響 54
2、大豆蛋白對肝臟三酸甘油酯之影響 55
3、大豆蛋白對糞便三酸甘油酯和總脂肪之影響 58
4、大豆蛋白對血漿和肝臟總膽固醇與糞便固醇和膽酸之影響 59
五、大豆蛋白對於因酒精所造成之肝臟氧化壓力的影響 60
六、大豆蛋白對於因酒精所造成之肝臟發炎反應和纖維化的影響 62
七、單純酒精戒斷 (EC) 和酒精戒斷並給予大豆蛋白介入 (EP) 之比較 64
八、綜合討論 65
第五章 結論 66
參考文獻 67
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