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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳億乘 | |
dc.contributor.author | Yi-Chen Liu | en |
dc.contributor.author | 劉怡甄 | zh_TW |
dc.date.accessioned | 2021-06-16T13:32:04Z | - |
dc.date.available | 2023-07-19 | |
dc.date.copyright | 2013-08-08 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-07-19 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/62177 | - |
dc.description.abstract | 酒精濫用為引起致病率(morbility)及致死率(mortaility)的主要原因之一,根據世界衛生組織(World Health Organization, WHO)統計,2004年酒精濫用在全球所造成的死亡率即高達3.8%,而疾病負擔指標DALYs (Disability adjusted life-years)也高達4.6%,雖然自有紀錄以來,酒即為人類文化的一部分,但飲酒除了引起社會問題外,對健康亦有重大影響。
本實驗使用40隻八週齡雄性C57BL/6小鼠隨機分為五組:(1) control組:餵飼正常流質飼糧+管灌生理食鹽水;(2) EtOH組:餵飼酒精流質飼糧+管灌生理食鹽水;(3) ST1_1X:餵飼酒精流質飼糧+管灌1 mg Antrosterol (ergostatrien-3β-ol, ST1)/Kg BW;(4) ST1_5X:餵飼酒精流質飼糧+管灌5 mg ST1/Kg BW;(5) ST1_10X:餵飼酒精流質飼糧+管灌10 mg ST1/Kg BW,進行實驗的同時記錄小鼠採食量及體重變化,並於四週後犧牲小鼠採取其血清、肝臟及糞便進行分析。由結果發現,control體重與採食量皆顯著高於其他組別(p<0.05),補充ST1之組別,其體脂肪含量、血清及肝臟中脂質含量皆顯著低於EtOH組(p<0.05),顯示ST1可有效改善因酒精攝取造成的脂質累積,而肝臟損傷指標AST及ALT活性在補充ST1之組別也明顯低於EtOH組(p<0.05)。同時,補充ST1之組別其小鼠肝臟TBARS值顯著低於EtOH組,而抗氧化酵素活性及能力則顯著高於EtOH組(p<0.05),由此可知,ST1可有效改善肝臟氧化壓力並提升其抗氧化能力。在酒精代謝方面,補充ST1之組別有顯著較高的ADH活性(p<0.05),會導致自由基產生的CYP2E1其基因表現與蛋白質含量以及與血清中酒精濃度也顯著較EtOH組低(p<0.05)。導致肝臟發炎的TNF-α與IL-1β含量在補充ST1之組別中明顯低於EtOH組。由肝臟切片中可知,EtOH組其肝細胞之間出現了許多油滴空泡,肝臟外觀也較其他組別白,顯示了較多脂肪的累積,補充ST1之組別則可以改善脂質累積的現象。在基因表現方面,補充ST1之組別與EtOH組相較之下,脂質氧化相關之基因(PPAR-α, RXR-α, CPT1, and UCP2)表現有顯著的上升(p<0.05),脂質合成相關之基因(LXR-α, SREBP-1c, ACC, FAS, and ME)表現則顯著下降(p<0.05),而發炎與纖維化相關之基因(TLR4, MyD88, NF-κB, iNOS, COX-2, and α-SMA)表現明顯減少(p<0.05)。綜觀上述,ST1可藉由調節脂質恆定、抗氧化能力、酒精代謝及抗發炎能力來改善慢性酒精攝取對肝臟造成的傷害。 | zh_TW |
dc.description.abstract | Alcohol abuse is a major cause morbidity and mortality in the world. According to data from WHO, morbidity of alcohol abuse accounts for 4.6% DALYs (disability adjusted life-years) which is an indicator of disease burden and mortality of alcohol abuse is 3.8%. Although alcohol has been a part of human culture, alcohol consumption shows social and healthy problems.
Forty 8 week-old male B6 mice were used in the experiment and divided randomly into five groups: (1) control group: control liquid diet + normal saline; (2) EtOH group: ethanol liquid diet + normal saline; (3) ST1_1X: ethanol liquid diet + 1 mg antrosterol (ergostatrien-3β-ol, ST1)/Kg BW; (4) ST1_5X: ethanol liquid diet + 5mg ST1/Kg BW; (5) ST1_10X: ethanol liquid diet + 10mg ST1/Kg BW. After 4 weeks of experiment, supplementing ST1 reduced (p<0.05) serum and liver lipids in alcohol-fed mice while fecal lipid and bile acid outputs were increased (p<0.05). Supplementing ST1 promoted (p<0.05) hepatic antioxidant capability and lowered lipid peroxidation in alcohol-fed mice. Regarding the alcohol metabolism, alcohol-fed mice cotreated with ST1 had a higher (p<0.05) alcohol dehydrogenase (ADH) activity and gene expression of ADH, ALDH, and catalase; moreover, supplementing ST1 decreased (p<0.05) serum alcohol concentration and gene expression of CYP2E1. Western blot also showed that ST1 could reduce the protein content of CYP2E1. Lower (p<0.05) hepatic TNF-α and IL-1β contents were also measured in alcohol-fed mice cotreated with ST1. Moreover; a histological analysis (H&E staining) indicated that alcohol-fed groups existed clear and large lipid drops in livers but ST1 supplementation decreased them. Regarding the molecular mechanism of lipid homeostasis, ST1 upregulated (p<0.05) fatty acid oxidation, such as PPAR-α, RXR-α, CPT1, and UCP2, but downregulated (p<0.05) lipogenesis, such as LXR-α, SREBP1c, ME, ACC, and FAS. Besides, inflammation and fibrosis related genes, such as TLR4, MyD88, NF-κB, iNOS, COX-2, and α-SMA were downregulated (p<0.05) by supplementing ST1 as well. Based on current results, hepatoprotection of ST1 is attributed to its regulations of lipid homeostasis, antioxidant capability, alcohol metabolism, and anti-inflammation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T13:32:04Z (GMT). No. of bitstreams: 1 ntu-102-R00626026-1.pdf: 3327067 bytes, checksum: 1dd1c2dd8d97fc00b348979a2d6763c2 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 中文摘要 1
英文摘要 3 壹、前言 5 貳、文獻探討 7 2-1 肝臟結構 7 2-2 肝臟功能 10 2-2-1 醣類合成與代謝 10 2-2-2 蛋白質合成與代謝 11 2-2-3 脂質合成與代謝 11 2-2-4 膽汁分泌 11 2-2-5 儲存功能 12 2-2-6 解毒作用 12 2-2-6-1 超氧歧化酶(superoxide dismutase, SOD) 14 2-2-6-2 過氧化氫酶(catalase, CAT) 16 2-2-6-3 穀胱甘肽過氧化酶(glutathione peroxidase, GPx) 16 2-2-6-4 穀胱甘肽(glutathione, GSH) 17 2-3 酒 20 2-4 酒精性肝臟疾病(alcoholic liver disease, ALD) 20 2-4-1 酒精代謝 26 2-4-2 ALD與脂質變性(steatosis) 28 2-4-2-1 酒精對脂肪酸氧化系統的影響 28 2-4-2-2 酒精對脂肪酸合成的影響 30 2-4-3 ALD與氧化壓力 32 2-4-3-1 ALD中ROS的形成及損傷機制 32 2-4-4 ALD與發炎反應 36 2-5 牛樟芝(Antrodia camphorata)簡介 39 2-5-1 Antrosterol (ergostatrien-3β-ol, ST1) 41 參、材料與方法 44 3-1 實驗設計 44 3-2 實驗材料 45 3-3 動物飼養 45 3-4 樣本採集 47 3-5 實驗分析 47 3-5-1 小鼠肝臟損傷指標 47 3-5-2 小鼠體內脂質含量 48 3-5-2-1 小鼠血清三酸甘油酯濃度(triacylglycerol, TAG)分析 48 3-5-2-2 小鼠血清總膽固醇濃度(total cholesterol,TC)分析 49 3-5-2-3 小鼠肝臟脂質(TAG and TC)含量分析 49 3-5-2-4 小鼠糞便中脂質(TAG, TC, and bile acid)含量 50 3-5-3 小鼠肝臟氧化壓力及抗氧化能力評估 51 3-5-3-1 小鼠肝臟過氧化程度分析 51 3-5-3-2 小鼠肝臟總抗氧化能力(trolox equivalent antioxidant capacity, TEAC)分析 52 2-5-3-3 小鼠肝臟穀胱甘肽(glutathione, GSH)含量分析 52 3-5-3-4 小鼠肝臟超氧歧化酶(superoxide dismutase, SOD)活性分析 53 3-5-3-5小鼠肝臟過氧化酶(catalase, CAT)活性分析 54 3-5-3-6 小鼠肝臟穀胱甘肽過氧化酶(glutathione peroxidase, GPx)活性分析 54 3-5-4 小鼠肝臟代謝酒精能力分析 55 3-5-4-1 小鼠肝臟(cytochrome P450 2E1, CYP2E1)之蛋白質含量分析 55 3-5-4-2 小鼠肝臟酒精去氫酶(alcohol dehydrogenase, ADH)活性分析 56 3-5-4-3 小鼠肝臟乙醛去氫酶(acetaldehyde dehydrogenase, ALDH)活性分析 56 3-5-4-4 小鼠血清酒精濃度 57 3-5-5 小鼠肝臟發炎因子表現評估 57 3-5-5-1 小鼠肝臟腫瘤壞死因子-α (tumor necrosis factor-alpha, TNF-α)濃度分析 57 3-5-5-2 小鼠肝臟介白素-1β (interleukin-1β, IL-1β)濃度分析 58 3-5-6 小鼠肝臟結構切片 58 3-5-7 小鼠肝臟中特定基因之mRNA表現 59 3-6 統計分析 59 肆、結果與討論 63 4-1 小鼠生理參數變化 63 4-1-1 小鼠體重變化 63 4-1-2 小鼠採食量及各臟器相對重量 63 4-2 小鼠血清生化值分析 65 4-3 小鼠體內脂質恆定 65 4-3-1 小鼠血清中TAG及TC含量 65 4-3-2 小鼠肝臟中TAG及TC 66 4-3-3 小鼠糞便中TAG、TC及bile acid含量 66 4-4 小鼠體內氧化壓力及抗氧化能力 67 4-4-1 小鼠肝臟過氧化程度、總抗氧化能力及抗氧化物質含量 67 4-4-2 小鼠肝臟抗氧化酵素活性 68 4-5 小鼠肝臟發炎因子含量 69 4-6 小鼠肝臟酒精代謝能力 70 4-7 小鼠肝臟外觀及結構切片 71 4-8 小鼠特定基因之表現 72 4-8-1 小鼠肝臟調控脂質恆定相關之基因表現 72 4-8-2 小鼠肝臟發炎及纖維化相關之基因表現 73 4-9 不同動物模式下Antrosterol (ergostatrien-3β-ol, ST1)之保健功效 75 伍、結論 93 參考文獻 96 | |
dc.language.iso | zh-TW | |
dc.title | 發酵樟芝中Antrosterol在慢性酒精攝取下對肝臟保護功效 | zh_TW |
dc.title | Antrosterol from submerged fermentation
protects livers against chronic-alcohol-consumption injury | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 周崇熙,徐慶琳,楊登傑,邱智賢 | |
dc.subject.keyword | Antrosterol,酒精性肝臟疾病,脂質恆定,抗氧化,酒精代謝,抗發炎, | zh_TW |
dc.subject.keyword | Antrosterol,alcoholic liver disease,lipid homeostasis,antioxidant capability,alcohol metabolism,anti-inflammation, | en |
dc.relation.page | 118 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-07-19 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 動物科學技術學研究所 | zh_TW |
顯示於系所單位: | 動物科學技術學系 |
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