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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 潘子明 | |
| dc.contributor.author | Ting-Hung Chen | en |
| dc.contributor.author | 陳庭宏 | zh_TW |
| dc.date.accessioned | 2021-06-07T17:58:33Z | - |
| dc.date.copyright | 2012-08-15 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-10 | |
| dc.identifier.citation | Abbate, S. L., Brunzell, J. D. 1990. Pathophysiology of hyperlipidemia in diabetes mellitus. J Cardiovasc Pharmacol. 16 Suppl 9: S1-7.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16027 | - |
| dc.description.abstract | After the control of hepatitis viruses and westernization of the lifestyle in Taiwan, an increasing burden of nonalcoholic fatty liver disease (NAFLD) is anticipated and active prophylactic measures should be implemented. NAFLD is a clinicopathological term that encompasses a spectrum of abnormalities ranging from simple triglyceride accumulation in the hepatocytes to hepatic steatosis with inflammation, also known as nonalcoholic steatohepatitis (NASH). NASH can also progress to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, there are many types of medicines that are introduced to improve NAFLD, but none of them are specific for preventing or treating NAFLD in full aspects. The hypolipidemic and anti-inflammation effects of monascin (MS) and ankaflavin (AK) may indicate that they have potential to prevent or treat NAFLD. In the present study, we examined the oleic acid-induced steatosis effect in FL83B cell line treated with MS and AK. In vivo, the mice were fed with high-fat diet for NAFLD induction. Results showed that MS and AK reduced the steatosis effect in vitro and in vivo, and both in preventive and therapeutic models. Moreover, we discovered for the first time that the hypolipidemic effect of MS and AK may be achieved by sterol regulatory element binding protein and peroxisome proliferator-activated receptor alpha-related lipogenesis and fatty-acid oxidation pathways. Furthermore, MS and AK reduce the inflammatory cytokines in the liver tissue, which indicates that the metabolites may improve NAFLD by their hypolipidemic and anti-inflammation effects. | en |
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| dc.description.tableofcontents | VI
Contents Abbreviations ................................................................................................................... I 中文摘要 ........................................................................................................................ III Abstract ......................................................................................................................... IV Contents ......................................................................................................................... VI Figure Contents ............................................................................................................. XI Table Contents ........................................................................................................... XIV I. Introduction ................................................................................................................. 1 1. Discovery and taxonomy of Monascus spp. ......................................................... 1 2. History of Monascus ............................................................................................. 4 3. Secondary metabolites and multi-health improving effects of Monascus fermented products ................................................................................................... 8 3-1. Cholesterol synthesis inhibitors (monacolins) .......................................... 8 3-2. Pigments of Monascus ............................................................................ 10 3-3. γ-amino butyric acid (GABA) ................................................................. 14 3-4. Anti-cancer effects ................................................................................... 15 3-5. Blood glucose regulation ......................................................................... 16 3-6. Antioxidant properties ............................................................................. 17 3-7. Inhibition of Alzheimer amyloid protein deposition and improving VII learning and memory ...................................................................................... 17 3-8. Suppression of adipogenesis ................................................................... 18 4. Nonalcoholic fatty liver disease (NAFLD) ........................................................ 19 4-1. Nomenclature .......................................................................................... 20 4-2. Nature history of NAFLD ....................................................................... 23 4-3. NAFLD pathogenesis .............................................................................. 25 4-4. Treatments of NAFLD ............................................................................ 27 5. Genes in hepatic lipid metabolism that related to NAFLD ................................ 29 5-1. Lipogenesis-related genes ....................................................................... 29 5-2. FA oxidation (FAO)-related genes .......................................................... 30 5-3. FA transportation-related genes ............................................................... 33 6. Motives and goals ............................................................................................... 36 II. Materials and Methods ........................................................................................... 41 1. Reagents ............................................................................................................. 41 2. Equipments ......................................................................................................... 42 3. Solution preparation ........................................................................................... 43 3-1. Phosphate buffer saline (PBS) ................................................................. 43 3-2. Oil red O solution preparation ................................................................. 43 3-3. Others ...................................................................................................... 44 VIII 4. In vitro cell experiments ..................................................................................... 44 4-1. Cell culture condition .............................................................................. 44 4-2. Cell viability assay .................................................................................. 45 4-3. Oil red O stain ......................................................................................... 46 4-4. The steatosis related gene expression of FL83B ..................................... 47 4-4-1. Total RNA extraction with TRIzol reagent .................................. 47 4-4-2. Extracting total RNA from FL83B .............................................. 50 4-5. Reverse transcription (RT) of FL83B...................................................... 50 4-6. q-RT-PCR and gene analysis of FL83B cells .......................................... 51 4-6-1. Primers designed and synthesis ................................................... 51 4-6-2. Process of q-RT-PCR ................................................................... 52 4-7. Validating FL83B steatosis related genes by q-RT-PCR ......................... 52 5. In vivo animal experiments ................................................................................. 55 5-1. Establishment of animal model ............................................................... 55 5-1-1. Animal breeding ........................................................................... 55 5-1-2. Experimental groups and treatments ............................................ 55 5-2. Preparation of high-fat diet ..................................................................... 56 5-3. Biochemical analysis ............................................................................... 56 5-4. Cytokine analysis .................................................................................... 57 IX 5-5. Histological evaluation ............................................................................ 57 5-6. The Steatosis related gene expression of lever tissue ............................. 58 5-6-1. Total RNA extraction of liver tissue using TRIzol reagent ......... 58 5-7. Statistical analysis ................................................................................... 58 III. Results ..................................................................................................................... 59 1. In vitro experiments ............................................................................................ 59 1-1. Examination of sub-lethal dosages of monascin (MS) and ankaflavin (AK) by crystal violet staining assay ....................................................................... 59 1-2. Observation of lipid droplet formation by oil red O (ORO) stain ........... 59 1-2-1. Model one: MS and AK protect cells from OA-induced lipogenesis .............................................................................................. 59 1-2-2. Model two: MS and AK have recovery effect on OA-induced effects ...................................................................................................... 60 1-3. Validating the expression of seatosis-related genes by q-RT-PCR .......... 71 1-3-1. Expression of lipogenesis-related genes was down-regulated ..... 71 1-3-2. FAO-related mRNA expression were up-regulated in the therapeutic model ................................................................................... 74 1-3-3. Expression of FA transport-related genes is down-regulated ...... 78 2. In vivo experiments ............................................................................................. 80 X 2-1. Change in body weight, adipose tissue weight and liver weight of C57BL/6 mice ................................................................................................ 80 2-2. Effects of MS and AK on plasma fasting glucose level .......................... 83 2-3. Effects of MS and AK on plasma liver index levels ............................... 83 2-4. Effects of MS and AK on plasma lipid profiles ...................................... 84 2-5. Liver histopathological observations ...................................................... 90 2-6. Expression of hepatic genes related to steatosis in animal model........... 92 2-6-1. Expression of hepatic lipogenesis related genes were down-regulated ....................................................................................... 92 2-6-2. Expression of hepatic genes related to FAO ................................ 93 2-6-3. Expression of genes related to hepatic fatty acid transport were down-regulated ....................................................................................... 94 2-7. Effect of MS and AK on inflammatory cytokines production ................ 99 IV. Discussion and conclusion .................................................................................... 103 References ..................................................................................................................... 111 | |
| dc.language.iso | en | |
| dc.subject | ankaflavin | zh_TW |
| dc.subject | 脂肪變性肝炎 | zh_TW |
| dc.subject | 非酒精性脂肪肝 | zh_TW |
| dc.subject | 紅麴黃色素 | zh_TW |
| dc.subject | monascin | zh_TW |
| dc.subject | monascin (MS) | en |
| dc.subject | ankaflavin (AK) | en |
| dc.subject | nonalcoholic steatohepatitis (NASH) | en |
| dc.subject | nonalcoholic fatty liver disease (NAFLD) | en |
| dc.title | 探討紅麴二次代謝產物 monascin 和 ankaflavin對非酒精性脂肪肝之調控 | zh_TW |
| dc.title | Effects of the Monascus secondary polyketide metabolites, monascin and ankaflavin on regulation of nonalcoholic fatty liver disease | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蘇遠志,黃健雄,左克強,周涵怡 | |
| dc.subject.keyword | 脂肪變性肝炎,非酒精性脂肪肝,紅麴黃色素,monascin,ankaflavin, | zh_TW |
| dc.subject.keyword | nonalcoholic steatohepatitis (NASH),nonalcoholic fatty liver disease (NAFLD),monascin (MS),ankaflavin (AK), | en |
| dc.relation.page | 119 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2012-08-10 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
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