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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林璧鳳(Bi-Fong Lin) | |
dc.contributor.author | Yu-Chen Liu | en |
dc.contributor.author | 劉昱辰 | zh_TW |
dc.date.accessioned | 2021-06-16T17:14:46Z | - |
dc.date.available | 2017-08-27 | |
dc.date.copyright | 2012-08-27 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-08-19 | |
dc.identifier.citation | 康智雄 (2008) 影響3T3-L1細胞株分泌細胞激素之食材對高油飲食小鼠的免疫調節作用 國立台灣大學生化科技學系暨研究所 碩士論文
葉映君 (2008).具降NF-κB轉錄活性之食材對高油飲食小鼠血糖及發炎介質的影響國立台灣大學生化科技學系暨研究所 碩士論文 盧則豫 (2010) 松杉靈芝三萜類對高油飲食小鼠代謝症候群指標與發炎介質的影響 國立台灣大學生化科技學系暨研究所 碩士論文 呂佩諭 (2012) 山苦瓜水萃物及其區分物改善C56BL/6J公鼠高血糖之有效成分及機制探討 國立台灣大學生化科技學系暨研究所 博士論文 Abreu, M. T., Fukata, M., & Arditi, M. (2005). TLR signaling in the gut in health and disease. The Journal of Immunology, 174(8), 4453. Alberti, K. G., Zimmet, P., & Shaw, J. (2005). The metabolic syndrome--a new worldwide definition. Lancet, 366(9491), 1059. Arner, P. (1998). Not all fat is alike. Lancet, 351(9112), 1301. Broad, A., Kirby, J. A., & Jones, D. E. J. (2007). Toll-like receptor interactions: tolerance of MyD88-dependent cytokines but enhancement of MyD88-independent interferon-g production. Immunology, 120(1). doi: 10.1111/j.1365-2567.2006.02485.x Chan, L. L. Y., Chen, Q., Go, A. G. G., Lam, E. K. Y., & Li, E. T. S. (2005). 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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63610 | - |
dc.description.abstract | 肥胖已成為近年來重要的健康議題之一,肥胖者的脂肪組織被發現有脂肪細胞過度肥大以及巨噬細胞浸潤的情形,造成組織的慢性發炎,更進一步引起糖尿病、高血壓、高血脂等代謝異常的疾病。苦瓜為亞熱帶地區經常使用的草藥與食材,被發現具有降血糖、抗發炎以及降低體脂的功效。本實驗利用山苦瓜乙酸乙酯及水萃物,以Raw264.7巨噬細胞與3T3-L1脂肪細胞作為平台,探討山苦瓜萃物對於發炎反應以及脂質代謝的影響,評估山苦瓜是否具有改善肥胖以及肥胖引起的發炎反應。首先以山苦瓜萃物處理成熟脂肪細胞,觀察脂肪細胞脂解作用以及脂質代謝相關基因的表現,並測定上清液中細胞激素的分泌。接著探討山苦瓜萃物對巨噬細胞促發炎激素分泌的影響,最後將Raw264.7細胞以山苦瓜萃物預處理後再與3T3-L1共培養,觀察山苦瓜萃物是否透過影響巨噬細胞,進而改變脂肪細胞的發炎反應以及脂質代謝。
給予分化成熟3T3-L1脂肪細胞苦瓜乙酸乙酯萃物,可降低發炎激素MCP-1以及IL-6的分泌,減少細胞內脂質的累積,並增加脂肪酸氧化相關基因的表現。而以苦瓜水萃物處理的脂肪細胞,發炎激素分泌量上升,脂解作用增加,脂質生成及脂肪酸氧化的相關基因表現顯著下降。另一方面,山苦瓜乙酸乙酯萃物可降低巨噬細胞在LPS刺激下促發炎激素TNF-α及IL-6的分泌,相反的,山苦瓜水萃物會促進巨噬細胞促發炎激素的產生。綜合上述,山苦瓜乙酸乙酯萃物具有抗發炎的功效,相反的,水萃物則有促發炎的效果,而兩種萃物皆增加脂解作用的進行,可能具有減重的潛力。 進而將Raw264.7細胞以山苦瓜萃物預處理24小時,清洗細胞去除萃物後再與分化成熟3T3-L1脂肪細胞共培養,發現先給予Raw264.7細胞山苦瓜乙酸乙酯或水萃物,可減少共培養刺激之下巨噬細胞TNF-α的分泌,而山苦瓜萃物透過改變巨噬細胞也降低了脂肪細胞MCP-1的釋放以及兩者IL-6的分泌,並抑制脂肪細胞脂解作用的進行,減少引起發炎的游離脂肪酸,脂肪細胞發炎基因 COX-2的表現也被抑制,顯示在此細胞模式之下,山苦瓜萃物可透過影響巨噬細胞進而改變脂肪細胞的發炎反應與脂質代謝,具有潛力改善因肥胖而引起的慢性發炎。 | zh_TW |
dc.description.abstract | Obesity is often accompanied by several disorders, such as diabetes, hyperlipidemia, and hypertension. There is considerable evidence that obesity is a state of chronic low grade inflammation. Obese adipose tissue exhibits the inflammatory changes characterized by adipocyte hypertrophy and increased infiltration of macrophages. Bitter gourd (Momordica Charantia) is a tropical vegetable that has also been used in a traditional medicine for treating diabetes. In this study, the ethyl acetate (EA) and water extracts (WE) of bitter gourd powder (BGP) were used to determine the anti-obesity and anti-inflammatory effects on 3T3-L1 adipocytes, Raw264.7 macrophages and their interaction.
The pro-inflammatory cytokine secretions were examined after 24 hours treatment of BGP extracts. We showed that BGP-EA decreased the production of MCP-1 and IL-6 in 3T3-L1 adipocytes. TNF-α and IL-6 secretions in LPS-stimulated Raw264.7 was also inhibited. Inversely, BGP-WE elevated the production of pro-inflammatory cytokines both in 3T3-L1 and LPS-stimulated Raw264.7. On the other hand, Both BGP extracts stimulate basal lipolysis of 3T3-L1 after 24 hours treatment. The BGP-EA promoted the mRNA expression of β-oxidation factors. Unlike BGP-EA, BGP-WE suppressed the expression of lipogenic and β-oxidation factors in 3T3-L1. This study provides evidence for the anti-inflammatory effect of BGP-EA but pro-inflammatory effect of BGP-WE on macrophages and adipocytes. Increased lipolysis also suggested the anti-obesity effect of BGP extracts. To further investigate the interaction between adipocytes and macrophages, Raw 264.7 cells were pretreated with different concentrations of BGP-EA and BGP-WE then cocultured with 3T3-L1. Coculture of 3T3-L1 adipocytes and RAW 264.7 macrophages markedly enhanced lipolysis of adipocytes and the production of TNF-α, MCP-1 and IL-6 compared with control cultures. However, the secretion of these cytokines was decreased and lipolysis was inhibited when Raw264.7 cells were pretreated with BGP extracts. The mRNA expression of pro-inflammatory factors COX-2 was also diminished in 3T3-L1 adipocytes which were cocultured with BGP extracts-pretreated Raw264.7 cells. The inflammatory changes and the disorder of lipid metabolism induced by the interaction between adipocytes and macrophages were improved by the pretreatment of Raw264.7 with BGP extracts. The BGP may have potential to ameliorate the inflammation in obese adipose tissue. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T17:14:46Z (GMT). No. of bitstreams: 1 ntu-101-R99b22023-1.pdf: 1963169 bytes, checksum: 26617922b1e6f532ec8a7d1055acfb82 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 目錄
中文摘要 II 英文摘要 III 目錄 V 圖目錄 VIII 表目錄 XI 第一章 緒論 1 第一節 文獻回顧 1 一、白色脂肪組織 1 二、肥胖 4 三、PPAR連結脂質代謝與發炎反應 10 四、苦瓜 11 第二節 研究動機與架構 13 一、研究動機 13 二、研究架構 14 第二章 探討山苦瓜萃物對成熟3T3-L1脂肪細胞發炎反應與脂質代謝的影響 15 第一節 前言 15 第二節 材料與方法 16 一、山苦瓜萃取物製備 16 二、3T3-L1脂肪細胞株培養與分化 16 三、成熟3T3-L1樣品處理 19 四、細胞存活率分析 (DNA定量法) 19 五、細胞三酸甘油酯含量測定 20 六、甘油測定 21 七、非酯化游離脂肪酸測定 22 九、Real-time PCR分析細胞相關基因表現 23 十、統計方法 26 第三節 結果 27 一、山苦瓜萃物對成熟3T3-L1脂肪細胞株存活率的影響 27 二、山苦瓜萃物對成熟3T3-L1脂肪細胞細胞發炎反應的影響 27 三、山苦瓜萃物對成熟3T3-L1脂肪細胞脂解作用的影響 27 四、山苦瓜萃物對成熟3T3-L1脂肪細胞其他脂質代謝相關基因表現的影響 28 第四節 討論 39 一、山苦瓜乙酸乙酯萃物對脂肪細胞發炎與脂質代謝的影響 39 二、山苦瓜水萃物對脂肪細胞發炎與脂質代謝的影響 41 三、山苦瓜乙酸乙酯及水萃物降低體脂的功效 42 四、總結 44 第三章 以巨噬細胞與脂肪細胞共培養的模式探討山苦瓜對發炎及脂質代謝的 影響 45 第一節 前言 45 第二節 材料與方法 46 一、山苦瓜萃取物製備 46 二、Raw 264.7 小鼠巨噬細胞株培養與樣品處理 46 三、苦瓜萃物添加方式與LPS活化對Raw264.7 細胞TNF-α分泌的影響 47 四、LPS活化與3T3-L1細胞對山苦瓜預培養Raw264.7 細胞TNF-α分泌的影響 48 五、Raw264.7巨噬細胞與成熟3T3-L1脂肪細胞共培養 49 六、細胞存活率分析 (DNA定量法) 50 七、甘油測定 50 八、非酯化游離脂肪酸測定 50 九、細胞激素含量測定 50 十、Real-time PCR 分析相關基因表現 50 十一、統計方法 50 第三節 結果 51 一、山苦瓜萃物對Raw264.7巨噬細胞株的影響 51 二、苦瓜萃物添加方式與LPS活化對Raw264.7 細胞TNF-α分泌的影響 51 三、LPS活化與3T3-L1細胞對山苦瓜預培養Raw264.7 細胞TNF-α分泌的影響 51 四、預處理山苦瓜萃物的巨噬細胞與脂肪細胞共培養對發炎反應的影響 52 五、預處理山苦瓜萃物的巨噬細胞與脂肪細胞共培養對3T3-L1脂質代謝的影響 52 第四節 討論 65 一、山苦瓜萃物可透過影響巨噬細胞進而改變脂肪細胞 65 二、預處理於山苦瓜萃物的Raw264.7巨噬細胞與成熟3T3-L1共培養後對脂肪細胞脂質代謝相關基因表現的影響 66 三、探討苦瓜水萃物對發炎反應的影響 67 第四章 綜合討論與總結 70 第一節 綜合討論 70 一、探討脂肪組織的發炎反應以及脂解作用所扮演的角色 70 第二節 總結 73 圖目錄 圖1.1 白色脂肪組織的代謝功能 3 圖1.2 脂肪組織發炎的分子機制 7 圖2.1 3T3-L1脂肪細胞的分化流程 18 圖2.2 山苦瓜乙酸乙酯萃物與水萃物 對成熟3T3-L1細胞存活率的影響 30 圖2.3 山苦瓜乙酸乙酯萃物和水萃物對成熟3T3-L1細胞激素MCP-1、IL-6和 adiponectin分泌的影響 31 圖2.4 山苦瓜乙酸乙酯萃物和水萃物對成熟3T3-L1發炎相關基因COX-2 mRNA表現量的影響 32 圖2.5 山苦瓜乙酸乙酯萃物和水萃物對成熟3T3-L1細胞三酸甘油酯含量的影響 32 圖2.6 山苦瓜乙酸乙酯萃物和水萃物對成熟3T3-L1細胞脂解作用的影響 33 圖2.7 山苦瓜乙酸乙酯萃物和水萃物對成熟3T3-L1細胞脂解作用基因Perilipin HSL和ATGL mRNA表現量的影響 34 圖2.8 山苦瓜乙酸乙酯萃物和水萃物對成熟3T3-L1脂質生成相關基因FAS和 ACS mRNA表現量的影響 35 圖2.9 山苦瓜乙酸乙酯萃物和水萃物對成熟3T3-L1脂肪酸運送和脂質生成相關基因aP2 和 LPL mRNA表現量的影響 36 圖2.10 山苦瓜乙酸乙酯萃物和水萃物對成熟3T3-L1脂肪酸氧化相關基因ACD 和CPT1 mRNA表現量的影響 37 圖2.11 山苦瓜乙酸乙酯萃物和水萃物對成熟3T3-L1 PPARγ表現量的影響 38 圖3.1 不同方式給予山苦瓜樣品與LPS對Raw264.7細胞TNF-α分泌的影響 47 圖3.2 山苦瓜預處理的 Raw264.7細胞在有無LPS刺激下與3T3-L1共培養之實驗方法流程圖 48 圖3.3 Raw264.7巨噬細胞與3T3-L1脂肪細胞共培養的方法與流程 49 圖3.4 山苦瓜乙酸乙酯萃物和水萃物對Raw264.7細胞存活率的影響 54 圖3.5 山苦瓜乙酸乙酯萃物和水萃物對Raw264.7細胞促發炎激素TNF-α和 IL-6分泌的影響。 55 圖3.6 不同方式給予BGP-EA與LPS刺激對Raw264.7細胞TNF-α分泌的影響 56 圖3.7 不同方式給予BGP-WE與LPS刺激對Raw264.7細胞TNF-α分泌的影響 57 圖3.8 山苦瓜水萃物預處理後的Raw264.7細胞在有無LPS活化下以及有無與3T3-L1細胞共培養下對TNF-α分泌量的影響 58 圖3.9 山苦瓜萃物預處理之Raw264.7細胞與成熟3T3-L1細胞共培養對細胞激素TNF-α、MCP-1和IL-6分泌的影響 59 圖3.10 山苦瓜萃物預處理之Raw264.7細胞與成熟3T3-L1細胞共培養對adiponectin分泌的影響 60 圖3.11山苦瓜萃物預處理之Raw264.7細胞與成熟3T3-L1細胞共培養對3T3-L1發炎相關基因表現量的影響 60 圖3.12 山苦瓜萃物預處理之Raw264.7細胞與成熟3T3-L1細胞共培養對脂解作用的影響 61 圖3.13 山苦瓜萃物預處理之Raw264.7細胞與成熟3T3-L1細胞共培養對 3T3-L1脂解作用相關基因perilipin、HSL及ATGL表現量的影響 62 圖3.14 山苦瓜萃物預處理之Raw264.7細胞與成熟3T3-L1細胞共培養對 3T3-L1脂肪酸運送與脂質生成相關基因FAS、ACS、aP2、LPL表現量的影響 63 圖3.15山苦瓜萃物預處理之Raw264.7細胞與成熟3T3-L1細胞共培養對3T3-L1 PPARγ表現量的影響 64 表目錄 表1.1 adipokines對脂質代謝的影響 9 表2.1 山苦瓜萃物對3T3-L1脂肪細胞發炎反應與脂質代謝影響總整理 44 表3.1 整理Raw264.7巨噬細胞株與脂肪細胞株共培養下發炎介質的分泌情形 66 表4.1 山苦瓜萃物對Raw264.7巨噬細胞與3T3-L1脂肪細胞株發炎反應和脂質代謝之影響結果總整理表 72 | |
dc.language.iso | zh-TW | |
dc.title | Raw264.7巨噬細胞株預處理山苦瓜萃物影響3T3-L1脂肪細胞株的發炎介質分泌和脂質代謝 | zh_TW |
dc.title | Effects of Raw264.7 macrophages pretreated with Momordica charantia L. extracts on inflammatory mediators secretion and lipid metabolism of 3T3-L1 adipocytes | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃青真(Ching-jang Huang),江伯倫(Bor-Luen Chiang),吳文勉(Wen-Mein Wu),陳妙齡(Miaw-Ling Chen) | |
dc.subject.keyword | 脂肪細胞,巨噬細胞,山苦瓜,發炎,脂解作用, | zh_TW |
dc.subject.keyword | bitter gourd,adipocytes,macrophages,inflammation,lipolysis, | en |
dc.relation.page | 83 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-08-20 | |
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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