請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/93599完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 潘敏雄 | zh_TW |
| dc.contributor.advisor | Min-Hsiung Pan | en |
| dc.contributor.author | 周郁庭 | zh_TW |
| dc.contributor.author | Yu-Ting Chou | en |
| dc.date.accessioned | 2024-08-06T16:11:17Z | - |
| dc.date.available | 2024-08-07 | - |
| dc.date.copyright | 2024-08-06 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-07-30 | - |
| dc.identifier.citation | Abdi, H., & Williams, L. J. (2010). Principal component analysis. WIREs Computational Statistics, 2(4), 433-459.
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Remodeling of the gut microbiome by Lactobacillus johnsonii alleviates the development of acute myocardial infarction. Frontiers in Microbiology, 14, 1140498. Zhu, L., Zhang, D., Zhu, H., Zhu, J., Weng, S., Dong, L., Liu, T., Hu, Y., & Shen, X. (2018). Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe(-/-) mice. Atherosclerosis, 268, 117-126. Zhu, W., Gregory, J. C., Org, E., Buffa, J. A., Gupta, N., Wang, Z., Li, L., Fu, X., Wu, Y., Mehrabian, M., Sartor, R. B., McIntyre, T. M., Silverstein, R. L., Tang, W. H. W., DiDonato, J. A., Brown, J. M., Lusis, A. J., & Hazen, S. L. (2016). Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell, 165(1), 111-124. Zhu, Y., Li, Q., & Jiang, H. (2020). Gut microbiota in atherosclerosis: focus on trimethylamine N-oxide. Acta Pathologica, Microbiologica, et Immunologica Scandinavica, 128(5), 353-366. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/93599 | - |
| dc.description.abstract | 根據美國心臟學會統計，全球心血管疾病死亡人數逐年攀升，至 2021 年已上升至 1991 萬人，因此全球應更密切關注心血管疾病相關議題。動脈硬化為心血管疾病前期進程，研究發現腸道菌代謝產物氧化三甲胺 (Trimethylamine-N-oxide, TMAO)，會藉由多條路徑促進動脈硬化形成。TMAO 形成來源，為人體攝取富含肉鹼、膽鹼或甜菜鹼等飲食，這些物質在大腸中被含有特定代謝酵素基因 cutC/D、cntA/B 及 yeaW/X 之菌種代謝為三甲胺 (Trimethylamine, TMA)，再至肝臟中被 Flavin monooxygenase 3 (FMO3) 酵素轉化為 TMAO。先前已有研究證實多甲氧基黃酮 (Polymethoxyflavone, PMF) 可降低 TMAO 形成，減緩動脈硬化。PMF 為柑橘皮中，主要具生物活性之成分。因此本實驗以柑橘皮萃取物作為樣品，目的為探討柑橘皮萃取物對肉鹼飲水誘導小鼠心血管疾病之影響，期望開發潛在的新型健康食品。實驗利用 ApoE-/- 小鼠探討樣品對腸道菌相及減緩斑塊形成之效果。研究結果顯示，低劑量樣品組 (CLPM) 可顯著減少 carnitine 代謝並降低血液 TMAO 含量、增加糞便 carnitine 的排出。而高劑量樣品組 (CHPM) 降低 TMAO 生成之效果較弱。在氧化低密度脂蛋白 (oxLDL) 與動脈脂質堆積部分，低高劑量樣品皆可顯著提升血清 oxLDL 及降低動脈脂質堆積。除此之外，低高劑量樣品也能顯著減緩肝臟 FMO3 酵素表現量。在泡沫細胞生成路徑、PERK 接受器及發炎因子 mRNA 表現量，CLPM 組同樣可顯著降低相關基因表現量，而 CHPM 效果未如 CLPM 顯著。最後腸道菌方面，低高劑量樣品可顯著減少糞便中，特定代謝基因 cntA 及 yeaW 之表現量。而誘導組與控制組相比，腸道菌相組成迥異。給予低劑量樣品會使腸道菌相改變，與誘導組相比，CLPM 減少與促進 TMAO 生成相關之 Prevotella，增加有益菌 Bacteroides、Lactobacillus、Akkermansia。而高劑量樣品無法有效改善腸道菌相組成，其腸道菌群與誘導組相近。總結上述結果，低劑量樣品的介入可顯著降低血液 TMAO、特定基因 mRNA 表現量、減緩動脈脂質堆積、調控腸道菌相並增加有益菌之豐富度，說明低劑量樣品可減緩 carnitine 誘導之動脈病灶形成。高劑量樣品介入之組別，其 TMAO 含量、特定 mRNA 表現量無顯著差異，且腸道菌相調控能力較弱，但在減緩動脈脂質堆積有顯著效果，推測可能原因為高劑量樣品抑制有益菌生長，但可能透過其他途徑影響脂質堆積，原因尚需進一步探討。本次實驗結果證實，柑橘皮萃取物可望作為預防心血管疾病健康食品之開發新導向。 | zh_TW |
| dc.description.abstract | According to American Heart Association statistics, deaths from cardiovascular disease (CVD) rose to 19.91 million in 2021, indicating that the mortality rate of CVD has climbed year by year. This trend highlights the need for a greater focus on cardiovascular health. Atherosclerosis, an inflammatory disease of the large arteries, is a major cause of CVD and stroke. Recent research has identified trimethylamine-N-oxide (TMAO) as a novel and independent risk factor for promoting atherosclerosis. Dietary choline, carnitine, and betaine are metabolized into trimethylamine (TMA) by gut microbiota, and TMA is subsequently converted to TMAO by the hepatic enzyme flavin monooxygenase 3 (FMO3). Studies suggest that polymethoxyflavone (PMF) can reduce TMAO formation. In this context, citrus peel extract, which contains the bioactive compound PMF, was investigated for its ameliorative effect on carnitine-induced CVD in mice. The experiment sought to investigate the regulatory effect of citrus peel on intestinal bacteria to mitigate cardiovascular disease in mice, focusing on arterial plaque formation. The results revealed that the low dosage PMF (CLPM) significantly reduced carnitine metabolise and decreased blood TMAO levels, and increased fecal carnitine levels. However, the high dosage PMF (CHPM) only showed weaker ability to reduce TMAO. Both groups demonstrated an increase in plasma oxLDL levels and a reduction in lipid accumulation in aortic arches. Also, reduced the expression of liver FMO3. Additionally, the CLPM group was able to attenuate foam cell formation by inhibiting the CD36/LYN/JNK pathway, PERK receptor, and inflammation-related gene expression in the aorta. And the expression of fecal specific metabolic genes cntA and yeaW, were significantly reduced in CLPM and CHPM group. In terms of gut microbiota composition, the induced group exhibited significant changes compared to the control group. The CLPM group inhibited the growth of the negative bacterium Prevotella and increased the presence of beneficial bacteria such as Bacteroides, Lactobacillus, and Akkermansia. However, the CHPM group displayed a gut microbiota composition similar to that of the induced group in β diversity. In summary, 1% PMF significantly attenuated plasma TMAO levels, specific gene relative mRNA expression, lipid accumulation in aortic arches, and promoted the abundance of healthy bacteria. The 2.5% PMF dosage had a lesser effect on plasma TMAO levels, mRNA expression, and gut microbiota composition but still reduced lipid accumulation in the aorta. It is speculated that a high dosage of PMF may inhibit beneficial bacteria or affect lipid accumulation through alternative pathways. These findings suggest that citrus peel extract may be a promising direction for developing functional foods to prevent cardiovascular diseases. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-06T16:11:17Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-06T16:11:17Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 謝誌 I
中文摘要 IV Abstract VI Graphical Abstract VIII 目次 IX 附圖目次 XIII 附表目次 XIV 圖目次 XV 表目次 XVI 縮寫表 XVII 第一章、 文獻回顧 1 第一節、 心血管疾病 (Cardiovascular disease, CVD) 1 第二節、 動脈硬化 (Atherosclerosis) 2 (一)、 定義 2 (二)、 成因 3 (三)、 治療及預防 5 第三節、 動脈硬化與 TMAO 6 (一)、 TMAO 生成來源及途徑 6 (二)、 TMAO 造成動脈硬化路徑 7 第四節、 泡沫細胞形成與 TMAO 10 (一)、 單核球分化及巨噬細胞種類 10 (二)、 膽固醇平衡與泡沫細胞形成 10 (三)、 TMAO 對 CD36 之影響 11 第五節、 TMAO 與腸道菌相 12 第六節、 植化素與 TMAO 14 第七節、 柑橘類水果 (Citrus fruits) 15 (一)、 柑橘簡介 15 (二)、 多酚與類黃酮 16 (三)、 類黃酮與心血管疾病 16 第二章、 研究目的與實驗架構 18 第一節、 研究目的 18 第二節、 實驗架構 19 第三章、 材料與方法 20 第一節、 實驗材料 20 (一)、 儀器設備 20 (二)、 藥品試劑 21 (三)、 分析套組 23 (四)、 抗體 23 (五)、 qPCR 使用之引子 (primer) 23 (六)、 樣品來源 24 第二節、 動物實驗 (in vivo) 方法 26 (一)、 動物品系與飼養環境 26 (二)、 動物實驗組別設計 26 (三)、 飼料配製 27 (四)、 氧化三甲胺及肉鹼 (TMAO and carnitine) 含量測定 28 (五)、 動物犧牲 31 (六)、 血清生化數值分析 (Serum biochemistry) 31 (七)、 組織石蠟包埋及切片 (Paraffin embedded and section) 31 (八)、 組織冷凍包埋及切片 (Forzen embedded and section) 32 (九)、 組織蘇木精-伊紅染色 (Hematoxylin and Eosin staining) 33 (十)、 組織油紅染色 (Oil red o staining) 34 (十一)、 血清氧化低密度膽固醇 (Oxidized low-density lipoprotein, oxLDL) 含量測定 35 (十二)、 肝臟三酸甘油酯 (Triacylglycerol, TG) 含量測定 36 (十三)、 蛋白質定量 38 (十四)、 西方墨點法 (Western blotting) 39 (十五)、 微生物全長 16S 擴增子定序分析 (Full-Length 16S Amplicon Sequencing) 43 (十六)、 組織均質及 mRNA 萃取 44 (十七)、 RNA品質管控 (Quality control) 46 (十八)、 即時定量聚合酶連鎖反應 (Real-time polymerase chain reaction, qPCR) 49 第三節、 統計分析 51 第四章、 結果與討論 52 第一節、 PMF 對肉鹼飲水誘導小鼠動脈病灶之影響 52 (一)、 PMF 對肉鹼飲水誘導 ApoE-/- 血液糞便代謝物含量之影響 52 (二)、 PMF 對肉鹼飲水誘導 ApoE-/- 體重、攝食及飲水量之影響 57 (三)、 PMF 對肉鹼飲水誘導 ApoE-/- 小鼠臟器外觀及重量之影響 59 (四)、 PMF 對肉鹼飲水誘導 ApoE-/- 小鼠血液膽固醇之影響 61 (五)、 肉鹼飲水誘導對 ApoE-/- 小鼠三酸甘油脂之影響 63 (六)、 PMF 對肉鹼飲水誘導 ApoE-/- 小鼠臟器傷害之影響 65 (七)、 PMF 對肉鹼飲水誘導 ApoE-/- 小鼠血清 OxLDL 之影響 68 (八)、 PMF 對肉鹼飲水 ApoE-/- 小鼠動脈切片油紅染色之影響 69 第二節、 PMF 減緩動脈病灶之相關機制 72 (一)、 PMF 對肉鹼飲水 ApoE-/- 小鼠肝臟 FMO3 酵素表現影響 72 (二)、 PMF 對肉鹼飲水 ApoE-/- 動脈泡沫細胞相關基因表現影響 74 (三)、 PMF 對肉鹼飲水 ApoE-/- 小鼠動脈 PERK 接受器及發炎相關基因表現之影響 76 第三節、 PMF 調控肉鹼飲水誘導小鼠之腸道菌相 79 (一)、 PMF 對肉鹼飲水誘導 ApoE-/- 小鼠糞便特定代謝酵素基因之影響 79 (二)、 PMF 對小鼠腸道菌相 β 多樣性之影響 81 (三)、 PMF 對小鼠腸道菌相優勢物種氣泡圖之影響 84 (四)、 PMF 對小鼠物種相對豐度排名之影響 86 (五)、 PMF 對小鼠腸道菌相組間 Biomarkers 熱聚圖之影響 88 (六)、 小鼠腸道菌相組間差異物種與疾病之相關性 90 第五章、 結論 97 參考文獻 98 附錄 113 (一)、 預試實驗 113 (二)、 柑橘皮萃取物 PMFs 分析條件及圖譜 119 (三)、 血液糞便代謝物 TMAO 及 Carnitine 分析圖譜 121 (四)、 國立台灣大學動物實驗申請同意書 122 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 柑橘皮萃取物 | zh_TW |
| dc.subject | 腸道菌相 | zh_TW |
| dc.subject | 動脈硬化 | zh_TW |
| dc.subject | 氧化三甲胺 | zh_TW |
| dc.subject | 多甲氧基黃酮類 | zh_TW |
| dc.subject | Polymethoxyflavones | en |
| dc.subject | Atherosclerosis | en |
| dc.subject | Citrus peel extract | en |
| dc.subject | Gut microbiota | en |
| dc.subject | Trimethylamine-N-oxide | en |
| dc.title | 柑橘皮萃取物改善肉鹼飲水誘導 ApoE-/- 小鼠 TMAO 生成及相關之動脈病灶 | zh_TW |
| dc.title | Citrus peel extracts improve carnitine-induced TMAO production related to aorta lesion in ApoE -/- mice | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 何元順;黃步敏;羅翊禎;魏宗德 | zh_TW |
| dc.contributor.oralexamcommittee | Yuan-Soon Ho;Bu-Miin Huang;Yi-Chen Lo;Tzong-Der Way | en |
| dc.subject.keyword | 柑橘皮萃取物,多甲氧基黃酮類,氧化三甲胺,動脈硬化,腸道菌相, | zh_TW |
| dc.subject.keyword | Citrus peel extract,Polymethoxyflavones,Trimethylamine-N-oxide,Atherosclerosis,Gut microbiota, | en |
| dc.relation.page | 122 | - |
| dc.identifier.doi | 10.6342/NTU202402477 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2024-08-01 | - |
| dc.contributor.author-college | 生物資源暨農學院 | - |
| dc.contributor.author-dept | 食品科技研究所 | - |
| dc.date.embargo-lift | 2029-07-28 | - |
| 顯示於系所單位： | 食品科技研究所 | |
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