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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 丁詩同 | zh_TW |
| dc.contributor.advisor | Shih-Torng Ding | en |
| dc.contributor.author | 郭蕙瑄 | zh_TW |
| dc.contributor.author | Hui-Hshuan Kuo | en |
| dc.date.accessioned | 2024-08-20T16:20:19Z | - |
| dc.date.available | 2024-08-21 | - |
| dc.date.copyright | 2024-08-20 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-08-08 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94874 | - |
| dc.description.abstract | 非酒精性脂肪肝病 (nonalcoholic fatty liver disease, NAFLD) 為全球最常見的肝病之一，從單純的脂肪變性到發炎的非酒精性脂肪肝炎 (non-alcoholic steatosis hepatitis, NASH)，甚至再演變成肝硬化或肝癌。有許多天然的黃酮類化合物能透過改善發炎、氧化壓力和脂質代謝來達到護肝的效果，rhamnocitrin和ombuin為植物中常見的兩種黃酮類化合物，近年來，有許多研究指出它們具有出色的抗發炎和抗氧化的生物活性，但其在 NAFLD 作用的研究相對少。因此，本試驗旨在探討 rhamnocitrin 和 ombuin 對模擬NAFLD的脂肪肝細胞的影響，尤其是其對降低肝臟細胞脂肪堆積和抗氧化抗發炎的機制。
本試驗分別探討 rhamnocitrin 和 ombuin 對細胞脂質代謝及發炎反應的影響，利用 500 µM 的油酸來誘導人肝癌細胞株SK-HEP-1和HepG2 以及雞隻初代肝臟細胞的脂質堆積，細胞經過不同濃度的rhamnocitrin和ombuin處理後，進行紅油染色和測定三酸甘油酯的含量，以探討rhamnocitrin和ombuin是否具有減少肝細胞脂質堆積的效果，並進一步分析脂質合成和脂質分解相關基因的表現，以了解rhamnocitrin和ombuin 影響細胞脂質堆積的相關機制。另一方面，利用 100 µM 的棕櫚酸來誘導人肝癌細胞株SK-HEP-1和HepG2 以及雞隻初代肝臟細胞的氧化壓力和發炎反應，細胞經過不同濃度的rhamnocitrin和ombuin處理後，進行 ROS 含量的測定，並進一步分析發炎反應相關基因的表現，以了解rhamnocitrin和ombuin 影響細胞發炎反應的相關機制。 試驗結果顯示，rhamnocitrin和ombuin 的處理能顯著的降低紅油染色的染色面積 (P<0.05)，同時也能顯著降低油酸所誘導的總三酸甘油酯含量 (P<0.05)，進一步分子機制的研究顯示 rhamnocitrin和ombuin 能夠透過增加 AMP activated protein kinase (AMPK) 的活性，顯著增加脂質氧化相關基因 peroxisome proliferator activated receptor α (PPARα) 和 carnitine palmitoyl transferase 1a (CPT1a) 的 mRNA 及蛋白質的表現量 (P<0.05)，顯示會因此等處理增加細胞脂肪酸的分解；此二處理也同時降低脂質生合成相關基因 sterol regulatory element binding protein 1c (SREBP1c)、acetyl CoA carboxylase (ACC) 和 fatty acid synthase (FAS) 的mRNA 及蛋白質的表現量 (P<0.05)，因而會減少細胞脂質生合成的作用，最終達到減少細胞脂質堆積的效果。另一方面，rhamnocitrin和ombuin 的處理能夠顯著的降低棕櫚酸所誘導的細胞 ROS含量 (P<0.05)，減少細胞的氧化壓力。此外，rhamnocitrin和ombuin 能夠透過增加 AMPK 的活性，增加nuclear factor kappa-B (NF-κB) 的抑制因子IκB的表現，顯著抑制 NF-κB 活性，因而降低其下游促發炎因子tumor necrosis factor-α (TNFα)、interleukin 6 (IL-6) 和 interleukin-1β (IL-1β) 的表現量 (p<0.05)，顯示此等處理也可降低細胞的發炎反應。 綜上所述，rhamnocitrin和ombuin 透過活化 AMPK 的活性，調節脂質代謝和發炎反應相關基因的表現，促進脂質分解和抑制脂質生合成的作用，最終達到減少細胞脂質堆積和發炎的效果。 | zh_TW |
| dc.description.abstract | Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, ranging from simple steatosis to inflammatory non-alcoholic steatohepatitis (NASH), and even progresses into cirrhosis or liver cancer. Natural flavonoids can achieve hepatoprotective effects by improving inflammation, oxidative stress, and lipid metabolism. Rhamnocitrin and ombuin are two common flavonoids found in plants. Recent studies have indicated their outstanding effects as anti-inflammatory and antioxidant bioactivities, but their effects on NAFLD are relatively understudied. Therefore, this study aims to investigate the effects of rhamnocitrin and ombuin on simulated NAFLD fatty liver cells, particularly for their mechanisms in reducing hepatic lipid accumulation and exerting antioxidant and anti-inflammatory effects.
This study explored the effects of rhamnocitrin and ombuin on cellular lipid metabolism and inflammatory responses. Human liver cancer cell lines SK-HEP-1 and HepG2, as well as primary chicken hepatocytes, were induced with 500 µM oleic acid for lipid accumulation. After treatment with various concentrations of rhamnocitrin and ombuin, the cells were subjected to Oil red O staining and triglyceride content measurement. Further analysis of lipid metabolism-related genes expression were conducted to understand the mechanisms by which rhamnocitrin and ombuin affect cellular lipid accumulation. In another aspect, cells were induced with 100 µM palmitic acid to trigger oxidative stress and inflammatory responses. After treatment with different concentrations of rhamnocitrin and ombuin, ROS production was measured, and the expressions of inflammation-related genes were analyzed to understand how rhamnocitrin and ombuin affect cellular inflammatory responses. The results showed that treatment with rhamnocitrin and ombuin significantly reduced the stained area in Oil red O staining (P<0.05) and significantly decreased the total triglyceride content induced by oleic acid (P<0.05). Further molecular mechanism studies revealed that rhamnocitrin and ombuin significantly increased the expression of β-oxidation related genes peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase 1a (CPT1a) at mRNA and protein levels (P<0.05) by activating AMP-activated protein kinase (AMPK), indicating an increase in cellular fatty acid oxidation. These treatments also reduced the mRNA and protein levels of de novo lipogenesis genes, sterol regulatory element-binding protein 1c (SREBP1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) (P<0.05), thereby decreasing lipid biosynthesis and ultimately reducing cellular lipid accumulation. Moreover, treatment with rhamnocitrin and ombuin significantly reduced palmitic acid-induced cellular ROS generation (P<0.05) to decrease cellular oxidative stress. Additionally, rhamnocitrin and ombuin increased the expression of the inhibitor of NF-κB (IκB) by activating AMPK, to inhibit nuclear factor kappa-B (NF-κB) activity and thus reduce the expression of downstream pro-inflammatory cytokines, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and interleukin-1β (IL-1β) (P<0.05), indicating a reduction in cellular inflammatory responses. In conclusion, rhamnocitrin and ombuin activated AMPK signaling, regulated the expression of genes related to lipid metabolism and inflammatory responses, promoted β-oxidation, and inhibited de novo lipogenesis, ultimately reducing cellular lipid accumulation and inflammation. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-20T16:20:18Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-20T16:20:19Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 I
中文摘要 II Abstract IV 目次 VI 圖次 IX 表次 XII Figure content XIII Table content XVI 壹、 文獻探討 1 一、 非酒精性脂肪肝病 1 (一) 非酒精性脂肪肝病 1 (二) 診斷與臨床表現 1 (三) 盛行率及高風險族群 3 (四) 病理機制 4 (五) 治療方法與困境 7 二、 家禽脂肪肝病 10 (一) 家禽脂肪肝病的起源與現況 10 (二) 家禽肝臟的脂肪代謝 10 (三) 病理症狀 11 (四) 致病因素 11 (五) 家禽與人類脂肪肝的關聯性 13 三、 脂肪肝病的研究模式 14 (一) 人類非酒精性脂肪肝病細胞模式 14 (二) 家禽脂肪肝病細胞模式 15 四、 Rhamnocitrin 和 Ombuin保護非酒精性脂肪肝病的潛在效果 16 (一) Rhamnocitrin 的生物活性 16 (二) Ombuin 的生物活性 17 五、 研究目的 18 貳、 試驗材料與方法 19 一、 試驗設計 19 二、 人類肝癌細胞培養與處理 19 三、 雞隻初代肝臟細胞培養與處理 20 四、 細胞存活率試驗 22 五、 細胞總三酸甘油酯測定 22 六、 細胞油紅染色 23 (一) 油紅染色 (Oil red O staining) 23 (二) 磺胺多巴酚B (Sulforhodamine B, SRB)細胞含量測定法 23 七、 活性氧物質 (ROS) 測定 23 八、 RNA 萃取與即時定量 PCR 分析 24 (一) 細胞 RNA 萃取 24 (二) 即時定量 PCR (Real-time PCR) 24 九、 西方墨點法（Western blotting） 25 十、 統計分析 26 參、 試驗結果 28 一、 試驗一：Rhamnocitrin 和 ombuin 對人類肝癌細胞脂肪堆積之影響 28 (一) 細胞存活率試驗與處理劑量 28 (二) 紅油染色 32 (三) 三酸甘油酯含量 39 (四) 脂質代謝相關基因表現 42 (五) AMPK 訊息傳導路徑及脂質代謝相關蛋白質表現 49 二、 試驗二：Rhamnocitrin 和 ombuin 對人類肝癌細胞氧化壓力及發炎反應之影響 59 (一) 細胞存活率試驗 59 (二) 活性氧物質含量 61 (三) 發炎反應相關基因表現 68 (四) AMPK 及 NF-κB 訊息傳導路徑 75 三、 試驗三： Rhamnocitrin 和 ombuin 對雞隻初代肝臟細胞脂肪堆積之影響 85 (一) 細胞存活率試驗 85 (二) 紅油染色 87 (三) 三酸甘油酯含量 91 (四) 脂質代謝相關基因表現及 AMPK 訊息傳導路徑 92 四、 試驗四： Rhamnocitrin 和 ombuin 對雞隻初代肝臟細胞氧化壓力及發炎反應之影響 100 (一) 細胞存活率試驗 100 (二) 活性氧物質含量 100 (三) 發炎反應相關基因表現及 AMPK 訊息傳導路徑 104 肆、 討論 109 一、 Rhamnocitrin 和 ombuin 緩解 NAFLD 細胞模式之脂肪堆積 109 (一) 脂質合成 109 (二) 脂質氧化 111 (三) AMPK 對脂質代謝的調節 112 二、 Rhamnocitrin 和 ombuin 緩解 NAFLD 細胞模式之氧化壓力及發炎反應 115 (一) 氧化壓力及發炎反應 115 (二) AMPK 對發炎反應的調節 116 三、 二甲雙胍 (Metformin) 119 伍、 結論 122 陸、 參考文獻 123 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | rhamnocitin | zh_TW |
| dc.subject | 非酒精性脂肪肝 | zh_TW |
| dc.subject | 發炎 | zh_TW |
| dc.subject | 脂質堆積 | zh_TW |
| dc.subject | ombuin | zh_TW |
| dc.subject | NAFLD | en |
| dc.subject | rhamnocitrin | en |
| dc.subject | ombuin | en |
| dc.subject | lipid accumulation | en |
| dc.subject | inflammation | en |
| dc.title | Rhamnocitrin 和 Ombuin降低肝臟細胞脂肪堆積下之抗氧化抗發炎的作用機制 | zh_TW |
| dc.title | The mechanisms of rhamnocitrin and ombuin against lipid accumulation-induced oxidative stress and inflammation in hepatocytes | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 林原佑;游玉祥;陳洵一 | zh_TW |
| dc.contributor.oralexamcommittee | Yuan-Yu Lin;Yu-Hsiang Yu ;Shuen-Ei Chen | en |
| dc.subject.keyword | 非酒精性脂肪肝,rhamnocitin,ombuin,脂質堆積,發炎, | zh_TW |
| dc.subject.keyword | NAFLD,rhamnocitrin,ombuin,lipid accumulation,inflammation, | en |
| dc.relation.page | 135 | - |
| dc.identifier.doi | 10.6342/NTU202403189 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2024-08-10 | - |
| dc.contributor.author-college | 生物資源暨農學院 | - |
| dc.contributor.author-dept | 動物科學技術學系 | - |
| dc.date.embargo-lift | 2025-08-31 | - |
| 顯示於系所單位： | 動物科學技術學系 | |
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