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標題: | 發酵樟芝中Antrosterol在慢性酒精攝取下對肝臟保護功效 Antrosterol from submerged fermentation protects livers against chronic-alcohol-consumption injury |
作者: | Yi-Chen Liu 劉怡甄 |
指導教授: | 陳億乘 |
關鍵字: | Antrosterol,酒精性肝臟疾病,脂質恆定,抗氧化,酒精代謝,抗發炎, Antrosterol,alcoholic liver disease,lipid homeostasis,antioxidant capability,alcohol metabolism,anti-inflammation, |
出版年 : | 2013 |
學位: | 碩士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/62177 |
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顯示於系所單位: | 動物科學技術學系 |
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