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???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
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dc.contributor.advisor | 陳燕惠(Yen-Hui Chen) | |
dc.contributor.author | Li-Hung Yang | en |
dc.contributor.author | 楊禮鴻 | zh_TW |
dc.date.accessioned | 2021-06-13T07:59:29Z | - |
dc.date.available | 2010-08-02 | |
dc.date.copyright | 2005-08-02 | |
dc.date.issued | 2005 | |
dc.date.submitted | 2005-07-22 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/36399 | - |
dc.description.abstract | 非典型抗精神病藥olanzapine為臨床上第一線的精神疾病用藥,目前被廣泛使用於治療躁症、鬱症等精神疾病。最主要的副作用為體重增加與血脂上升,造成病人順從性的降低與新血管疾病的危險性升高。目前通泛的解釋為阻斷5-HT2C、H1與促進5-HT1A受體引起的食量增加,但是詳細的機轉目前仍不清楚。本實驗利用3T3-L1前驅脂肪細胞分化的模式觀察到olanzapine可以加強細胞內三酸甘油脂的蓄積,並且增加fatty acid synthase與adiponectin的mRNA表現,機轉上可能是透過SREBP-1轉錄因子。利用報導基因的研究發現olanzapine除了能增加SREBP-1對於含有SRE-1 promoter的基因的轉錄能力外,也促進了SREBP-1的表現。在HepG2 肝細胞株上,也證明了olanzapine可以促進報導基因與SREBP-1的表現。本實驗結果發現olanzapine除了中樞神經的作用外,亦可能透過SREBP-1在脂細胞及肝細胞影響體內脂質的合成。 | zh_TW |
dc.description.abstract | Olanzapine is a second generation atypical antipsychotic drug, treating positive symptom, negative symptom, etc. The major side effects are weight gain and hyperglycemia. These effects reduce patient compliance and are risk factors of cardiac vascular disease. The possible mechanisms are poor satiety and increases in food intake induced by 5-HT2C, H1 receptor antagonists and 5-H1A agonists; the exact mechanisms are still unclear.
In the present study, we observed olanzapine increased triacylglyceride (TG) accumulation during 3T3-L1 preadipocyte differentiation, as well as the expression of fatty acid synthase and adiponectin. The effect may be regulated by SREBP-1, a major transcription factor in lipid homeostasis. Olanzapine enhances the activity of SRE-1-containing LDLR promoter in tranfected 3T3-L1 preadipocyte and HepG2 cell lines. Increase in SREBP-1 precursor form was as well observed. In conclusion, olanzapine may not only cause adiposity through CNS receptor, but also affect the peripheral lipogenic molecules regulated by SREBP-1. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T07:59:29Z (GMT). No. of bitstreams: 1 ntu-94-R91423022-1.pdf: 1042551 bytes, checksum: 6fb0bf0f816f32bbce48f296a0a5e9d2 (MD5) Previous issue date: 2005 | en |
dc.description.tableofcontents | 序論………………………………………………………………………1
第一節 非典型抗精神病藥物在體重和代謝的效應 ………………………………2 第二節 脂肪細胞分化的分子機制 …………………………………………………5 第三節 固醇調節元件結合蛋白(Sterol Regulatory Element Binding Proteins, SREBPs)………………………………………………………………………8 第四節 脂質新生(De Novo Lipogenesis)…………………………………………9 實驗材料與方法 ………………………………………………………11 第一節 實驗儀器……………………………………………………………………12 第二節 細胞培養與分化……………………………………………………………13 第三節 Olanzapine的萃取與分析………………………………………………14 第四節 Oil Red-O染色試驗 ………………………………………………………15 第五節 西方墨點法 Western blotting …………………………………………16 第六節 逆轉錄聚合酶連鎖反應法RT-PCR………………………………………20 第七節 冷光酵素報導基因分析法 Luciferase Gene Reporter Assay…………24 實驗結果………………………………………………………………27 第一節 Olanzapine促進3T3-L1前驅脂肪細胞的分化…………………………28 第二節 Olanzapine不改變PPAR-γ與CEBP-α細胞核蛋白的量………………29 第三節 Olanzapine促進adiponectin與fatty acid synthase mRNA的表現……………………………………………………………………………30 第四節 Olanzapine增加含SRE-1的LDLR promoter的活性……………………31 第五節 Olanzapine可增加SREBP-1a的表現……………………………………33 討論……………………………………………………………………34 第一節 實驗結果的討論……………………………………………………………35 第二節 Olanzapine活化SREBP-1路徑的可能性機轉探討………………………38 第三節 由pharmacokinetic的觀點討論olanzapine臨床上血中濃度與實驗濃度的相關性……………………………………………………………………40 第四節 由pharmacogenomic的觀點討論可能影響lipogenesis的基因變異…41 圖表……………………………………………………………………42 Figure 1 3T3-L1 differentiation protocol……………………………………………43 Figure 2 Morphological change and oil droplet accumulation………………………43 Figure 3 Cell differentiation detected by Oil Red-O staining and quanted by spectrophotometry on day 5…………………………………………………………44 Figure 4 Induction of PPAR-γ and C/EBP-α during the first 48 hours of 3T3-L1 preadipocyte differentiation…………………………………………………………45 Figure 5 PPAR-γ and C/EBP-α levels in nucleus on 24 hours after induction………46 Figure 6 mRNA expression of fatty acid synthase (FASN, panel A) and adiponectin (panel B) on 48 hours after induction of 3T3-L1 cells………………………………47 Figure 7 Luciferase assay of 24 hour drug treatment………………………………48 Figure 8 Olanzapine induces SREBP-1a expression…………………………………50 參考文獻………………………………………………………………51 附錄1………………………………………………………………………………A1 附錄2………………………………………………………………………………A3 附錄3………………………………………………………………………………A5 | |
dc.language.iso | zh-TW | |
dc.title | Olanzapine促進細胞脂質新生的機轉探討 | zh_TW |
dc.title | The mechanism of lipogenesis enhanced by olanzapine in cell lines | en |
dc.type | Thesis | |
dc.date.schoolyear | 93-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳擇銘,楊偉勛(Wei-Shiung Yang),黃宗正 | |
dc.subject.keyword | 脂肪細胞,脂質合成, | zh_TW |
dc.subject.keyword | olanzapine,lipogenesis,3T3-L1, | en |
dc.relation.page | 58 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2005-07-22 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥學研究所 | zh_TW |
Appears in Collections: | 藥學系 |
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