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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 王淑慧(Shu-Huei Wang) | |
| dc.contributor.author | You-Yu Liu | en |
| dc.contributor.author | 劉祐瑜 | zh_TW |
| dc.date.accessioned | 2023-03-19T23:57:08Z | - |
| dc.date.copyright | 2022-10-03 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-08-17 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/86460 | - |
| dc.description.abstract | 非酒精性脂肪肝(nonalcoholic fatty liver disease; NAFLD)是造成代謝綜合症和第二型糖尿病的主因，臨床主要病徵為代謝失調，如高血糖、高血脂症和胰島素阻抗。補骨脂寧(Corylin)是一種從補骨脂 (Psoralea corylifolia L.)萃取出的異黃酮類化合物，多項研究已證實Corylin具有抗氧化及抗發炎作用，並且可以降低肥胖和胰島素阻抗發生。然而，Corylin 對於肝臟代謝的調控作用及機制尚不清楚，因此本研究目的是探討 Corylin 對非酒精脂肪肝疾病的影響。首先，在細胞實驗中使用棕櫚酸 (Palmitic acid, PA) 誘導人類肝細胞 (HepG2) 進行研究；在動物實驗部分，利用高脂飼料誘導小鼠肥胖的模式，藉由同時餵食Corylin 10週，藉此探討Corylin對於NAFLD的作用，透過評估肝細胞中油滴累積、胰島素阻抗性和非酒精性脂肪肝疾病的相關生化數值和蛋白質表達量，觀察Corylin是否可以抑制非酒精性脂肪肝的形成。本篇研究結果顯示，在細胞實驗結果方面，Corylin 具有減少脂質合成、保護棕櫚酸誘導粒線體功能的失調、降低氧化性壓力(oxidative stress)、並增加肝細胞葡萄糖攝取的能力和胰島素敏感度。在動物實驗部分，Corylin的餵食也顯示能有效減少高脂飲食誘導小鼠的體重增加、改善胰島素敏感度、抑制肝臟油滴堆積和纖維化的嚴重程度。AMP active protein kinase (5' adenosine monophosphate-activated protein kinase, AMPK)參與多種生理代謝，在細胞能量穩定中發揮作用，在肝臟中負責調控脂質和醣類代謝，本篇研究結果顯示Corylin 藉由增加AMPK的活化，抑制肝細胞中經由PA造成的油滴累積，改善粒線體活性和減少ROS的產生。綜合上述結果，我們推測Corylin 可以作為改善非酒精性脂肪肝疾病的新治療藥物選擇。 | zh_TW |
| dc.description.abstract | Nonalcoholic fatty liver disease (NAFLD) is a major cause of metabolic syndrome and type II diabetes, and it presents with metabolic disorders, such as hyperglycemia, hyperlipidemia, and insulin resistance. Corylin, a flavonoid compound extracted from Psoralea corylifolia L., has been shown to have antioxidant, anti-inflammatory effects and can reduce obesity and insulin resistance. However, it remains unknown whether Corylin could modulate the metabolism of liver, so the objective of this study is to explore the effect of Corylin on NAFLD. The anti-NAFLD effects of Corylin on fat accumulation, insulin resistance, and NAFLD-related physiological parameters and protein levels were assessed in high-fat diet (HFD)-induced obese mice in vivo and in palmitate (PA)-treated HepG2 cells in vitro. The present study showed that Corylin strikingly increased insulin sensitivity, glycogen synthesis and reduced body weight, fat accumulation, reactive oxygen species (ROS) and fibrosis in HFD-treated mice. In addition, Corylin also decreased lipid synthesis and improved mitochondria dysfunction, glucose uptake ability and insulin sensitivity in PA-induced HepG2 cells. Corylin significantly decreased the expression of lipid metabolism-related proteins level and improved the expression of glucose metabolism-related proteins level. The above effects of Corylin on NAFLD inhibition were through AMP-activated protein kinase (AMPK) pathway. Based on the above results, we speculate that Corylin can be used as a new treatment option for NAFLD. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T23:57:08Z (GMT). No. of bitstreams: 1 U0001-1008202214421700.pdf: 5695195 bytes, checksum: ddb5f4331556e0828ae0d991b3447f04 (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 口試委員會審定書 I 誌謝 II 摘要 III Abstract IV 目錄 V 壹、 緒論 1 一. 前言 1 二. 肝臟的代謝作用 1 三. 非酒精性脂肪肝疾病 2 四. 粒線體受損與非酒精性脂肪肝疾病的關聯 3 五. 胰島素阻抗與非酒精性脂肪肝疾病的關聯 4 六. 非酒精性脂肪肝炎和肝纖維化 4 七. 非酒精性脂肪肝疾病中的訊息傳遞路徑 6 八. Corylin與非酒精性脂肪肝疾病的關聯 8 九. 研究動機和實驗設計 9 貳、 實驗材料 10 一. 儀器設備 10 二. 實驗材料 10 藥品 10 細胞培養 10 結晶紫染色分析(Crystal violet stain assay) 10 西方墨點法(Western blot) 10 Triglycerides (TRIGS)/ Cholesterol (CHOL) assay 12 Oil Red O染色 12 BODIPY stain 12 ROS活性氧化物偵測 12 Mitoview螢光染色 12 2-NBDG螢光檢測 12 肝醣測試 (Glycogen assay) 12 動物實驗 12 蛋白質萃取(Protein Extraction) 12 石蠟切片包埋 13 冷凍切片包埋 13 H&E stain 13 訊號核醣核酸(mRNA) 13 PAS肝醣染色試驗 (Periodic Acid Schiff stain) 13 天狼星紅苦味酸染色 (PicroSirius red/fast green stain) 14 三. 溶液配置 14 參、 實驗方法 15 一. 細胞實驗 15 細胞株之培養 15 結晶紫染色分析(Crystal violet stain assay) 15 Oil red O stain (ORO stain) 15 BODIPY stain 16 Mitoview staining 16 2-NBDG staining 16 Glycogen assay 17 二. 動物實驗 17 非酒精性脂肪肝小鼠模式 17 石蠟切片包埋 18 冷凍切片包埋 18 Oil red O stain (ORO stain) 18 葡萄糖耐受性測試(Intraperitoneal glucose tolerance test; IPGTT) 18 胰島素耐受性測試(Intraperitoneal insulin tolerance test; IPITT) 19 蘇木紫-伊紅染色 (Hematoxylin and Eosin stain) 19 天狼星紅苦味酸染色 (PicroSirius Red / Fast green stain) 19 PAS肝醣染色試驗 (Periodic Acid Schiff stain) 19 ROS 活性氧化物檢測 20 基因表現之測定 20 西方墨點法(Western blot) 21 數據統計分析 22 肆、 實驗結果 23 一. Corylin 可以抑制經由 PA誘導的HepG2細胞中的脂質堆積 23 二. Corylin 可以保護由PA誘導的肝細胞粒線體受損 24 三. Corylin 可以抑制PA誘導的肝細胞中ROS過量產生 24 四. Corylin 改善 PA 誘導肝細胞的胰島素阻抗(insulin resistance) 24 五. Corylin 改善肝醣合成和降低糖質新生作用 25 六. Corylin 具有減緩高脂飲食造成的肥胖作用 26 七. Corylin 改善各項代謝相關的生化值，並保護肝臟損傷 26 八. Corylin 抑制肥胖造成的肝脂肪變性 27 九. Corylin具有抑制脂肪酸生成相關mRNA和蛋白值的表達量 27 十. Corylin具有改善高血糖和胰島素阻抗的功用 28 十一. Corylin改善由高脂飲食引起的醣類代謝 29 十二. Corylin減緩肝臟中ROS的過量產生 29 十三. Corylin具有抑制脂肪性肝炎和減緩肝臟纖維化的作用 30 十四. Corylin 活化AMPK 30 十五. Corylin 藉由活化 AMPK 來抑制肝細胞中油滴的累積 31 十六. Corylin 藉由活化 AMPK 改善肝細胞中粒線體活性受損 31 十七. Corylin 藉由活化 AMPK 來抑制肝細胞中 ROS 的產生 32 伍、 討論 33 陸、 附圖 39 圖一、 Corylin 具有抑制由PA誘導的肝細胞中的油滴累積 39 圖二、 Corylin抑制脂肪酸相關蛋白質的增加 40 圖三、 Corylin具有改善粒線體受損的作用 41 圖四、 Corylin具有抑制ROS的產生的作用 42 圖五、 Corylin具有改善肝細胞胰島素阻抗的效果 43 圖六、 Corylin具有改善肝細胞吸收葡萄糖的作用 44 圖七、Corylin 具有改善 PA 誘導的肝醣合成減少和糖質新生作用增加的效 45 圖八、Corylin抑制高脂飲食小鼠的體重增加 46 圖九、Corylin對非酒精性脂肪肝小鼠的肝臟保護作用 47 圖十、 Corylin 有效抑制高脂飲食造成的肝臟油滴累積 48 圖十一、 Corylin有效抑制高脂飲食造成的肝臟脂肪酸生成相關蛋白的表現 49 圖十二、 Corylin 有效抑制高脂飲食造成的胰島素阻抗 50 圖十三、 Corylin 有效改善高脂飲食造成的肝醣合成下降 51 圖十四、 Corylin 有效抑制高脂飲食造成小鼠肝臟活性氧化物(ROS)的表現 52 圖十五、 Corylin 有效抑制高脂飲食造成的肝臟發炎因子相關蛋白的表現 53 圖十六、 Corylin有效抑制高脂飲食造成的小鼠肝臟纖維化 54 圖十七、 Corylin 顯著增加活化的AMPK蛋白質的表達量 55 圖十八、 探討Corylin對AMPK路徑機制的實驗設計圖 56 圖十九、 Corylin 活化AMPK抑制肝細胞油滴的累積 57 圖二十、 Corylin 藉由活化AMPK改善HepG2的粒線體活性 58 圖二十一、 Corylin 藉由活化AMPK抑制HepG2的ROS的產生 60 圖二十二、 Corylin 改善非酒精性脂肪肝疾病機制圖 61 表格一、 高脂飼料成分表 62 柒、 參考文獻 63 | |
| dc.language.iso | zh-TW | |
| dc.subject | 棕櫚酸 | zh_TW |
| dc.subject | 非酒精性脂肪肝疾病 | zh_TW |
| dc.subject | 棕櫚酸 | zh_TW |
| dc.subject | 補骨脂寧 | zh_TW |
| dc.subject | 非酒精性脂肪肝疾病 | zh_TW |
| dc.subject | 補骨脂寧 | zh_TW |
| dc.subject | NAFLD | en |
| dc.subject | Corylin | en |
| dc.subject | NAFLD | en |
| dc.subject | AMPK | en |
| dc.subject | ROS | en |
| dc.subject | palmitic acid | en |
| dc.subject | Corylin | en |
| dc.subject | AMPK | en |
| dc.subject | ROS | en |
| dc.subject | palmitic acid | en |
| dc.title | Corylin對於非酒精性脂肪肝疾病的治療作用和相關機制 | zh_TW |
| dc.title | The Therapeutic Effects and the Relative Mechanisms of Corylin on Nonalcoholic Fatty Liver Disease | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王仰高(Yang-Kao Wang),龔秀妮(Hsiu-Ni Kung) | |
| dc.subject.keyword | 補骨脂寧,非酒精性脂肪肝疾病,棕櫚酸, | zh_TW |
| dc.subject.keyword | Corylin,NAFLD,AMPK,ROS,palmitic acid, | en |
| dc.relation.page | 68 | |
| dc.identifier.doi | 10.6342/NTU202202259 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2022-08-17 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 解剖學暨細胞生物學研究所 | zh_TW |
| dc.date.embargo-lift | 2027-08-16 | - |
| Appears in Collections: | 解剖學暨細胞生物學科所 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| U0001-1008202214421700.pdf Until 2027-08-16 | 5.56 MB | Adobe PDF |
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