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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 龔秀妮(Hsiu-Ni Kung) | |
| dc.contributor.author | Shin-Yu Lai | en |
| dc.contributor.author | 賴欣妤 | zh_TW |
| dc.date.accessioned | 2021-06-15T11:30:57Z | - |
| dc.date.available | 2021-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-17 | |
| dc.identifier.citation | 1. ADA, http://www.diabetes.org/?referrer=https://www.google.com.tw/. 2016.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49485 | - |
| dc.description.abstract | 糖尿病是21世紀盛行率增加最快的代謝性疾病，根據世界衛生組織(WHO)統計全球目前糖尿病患者約有一億五千萬人，到2025年全球糖尿病患將增加為原本的一倍以上；糖尿病又分第一型(Insulin-dependent diabetes mellitus，IDDM)及第二型(Non- insulin-dependent diabetes mellitus，NIDDM)，由於現代飲食精緻化，罹患率增加的型態主要為第二型。台灣國民健康署指出，近年來糖尿病死亡率位居國人十大死因的前五名，其死亡原因不外乎是糖尿病導致的併發症：腎臟、心血管、神經病變等，而其中腎病變是導致死亡的主要併發症。
腎臟由許多不同種類的細胞組成，由腎絲球過濾單位(血管內皮細胞、基底膜、足細胞)、間質細胞及腎小管細胞維持腎臟的過濾代謝功能，糖尿病會導致腎臟細胞產生異常變化；在前人研究中得知糖尿病腎病變特徵主要為間質細胞擴張、變形及足細胞喪失貼附功能、肥大…等等使腎臟失去原有的過濾功能。 已有文獻證明在腎臟損傷成因中，氧化壓力的提高最為重要，本論文的研究目的是探討由一種樹皮中萃取出來的天然聚合物HN242在高脂飲食環境下是否能透過對抗氧化壓力，達到預防及治療糖尿病腎病變的效果。 本篇研究中使用長時間餵食高脂肪食物之模式誘發C57BL/6小鼠產生第二型糖尿病，預防組為吃高脂飼料同時餵食HN242；治療組為吃高脂飼料一段時間，測定血糖確診高血糖後再餵食HN242。透過腎臟組織切片染色及血液尿液分析等體內實驗及利用MES13腎間質細胞做體外實驗證實，HN242確實可以透過抗氧化及抗發炎等途徑達到保護及修復腎臟細胞的效果。因此，我們確信HN242對預防及治療高血糖導致之腎臟病變具極高的潛力。 | zh_TW |
| dc.description.abstract | The growing rate of diabetes mellitus (DM) is the highest in all the metabolic diseases in the 21st century. According to World Health Organization (WHO), there are about 150 million people with diabetes nowadays, and it is also the 5th leading death in 2014 in Taiwan according to the statistic of Ministry of Health and Welfare.
Two types of diabetes mellitus are defined. Type 1 diabetes (Insulin-dependent diabetes mellitus，IDDM) is usually diagnosed in children and teenagers who do not produce insulin. Type 2 diabetes (Non- insulin-dependent diabetes mellitus，NIDDM) is characterized by insulin resistance, and many lifestyle factors are known to be important in developing type 2 diabetes, including obesity. Patient with diabetes develops various complications that might cause death, and the major one is diabetic nephropathy. Kidney participates in whole-body homeostasis through filtration, reabsorption, and secretion, which take place in the nephron. Mesangial cells, podocytes and tubular epithelial cells play important roles in nephrons. Diabetic nephropathy leads to mesangial cell hypertrophy, podocyte loss and tubular epithelial cell damage or apoptosis, which results in filtration membrane failure and reabsorption dysfunction. The cause of diabetic nephropathy is well known for oxidative stress increase. This study aims to study whether HN242 , a nature compound extracted from the bark of tree in South America, can protect kidney from hyperglycemia-induced kidney disease by anti-oxidant ability. In the in vivo mouse model, HN242 was used to co-treat or post-treat with high-fat-diet for 70 or 35 days. With series of morphological observations, HN242 can decrease hyperglycemia-induced kidney damages, including basement membrane thicken, mesangial cell expansion, and podocyte process detachment. The filtration function loss of kidney caused by hyperglycemia is also recovered by HN242, and the reduction of inflammation and oxidative stress also be observed in kidney. For better dissection of the signaling pathway underlying how HN242 protects kidney from high fat-induced diabetes nephropathy, palmitate acid (PA) is used to treat MES 13 mouse mesangial cells in the in vitro cell model. HN242, either co-treat or post-treat with PA administration, can block the damages caused by PA through upregulating the anti-oxidant and anti-inflammation abilities. In conclusion, we suggest that HN242 may have great potential for both preventive and therapeutic use for diabetic nephropathy. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T11:30:57Z (GMT). No. of bitstreams: 1 ntu-105-R03446006-1.pdf: 6473130 bytes, checksum: 6cd984c01e166c3a7355c36eb887d52e (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 中文摘要………………………………………………………………………………………………………….………… i
英文摘要………………………………………………………………………………………………………………..…. ii 縮寫表…………………………………………………………………………………….………………………………. v 第一章 緒論………………………………………………………………1 第一節 引言………………………………………………………….……………………………………… 1 第二節 腎臟簡介……………………………………………………….…………..………1 第三節 糖尿病概況與簡介……………………………………………………….…………..………3 第四節 糖尿病診斷……………………………………………………………………………………….3 第五節 糖尿病與糖化血色素(HbA1c)指標關係……………………………………………3 第六節 糖尿病腎病變簡介…………………………………………………………………………..4 第七節 糖尿病腎病變與氧化壓力……………………………………………………………….5 第八節 氧化壓力與低氧環境、粒線體損傷的關係………….……………….…………6 第九節 氧化壓力與發炎反應的關係…………………………….……………………………..7 第十節 氧化壓力與醣類沉積、AGE與RAGE的關係…………………………………..8 第十一節 氧化壓力與自噬凋亡關係……………………………………………………………9 第十二節 糖尿病腎病變與血壓變化………………………………………………………………10 第十三節 糖尿病動物模式的發展………………………………………………………………….10 第十四節 研究目的…………………………………………………………………………………..……11 第二章 實驗材料與方法…………………………………………………………………..12 第一節 實驗藥品、動物與試劑來源………………………………………………………….12 第二節 動物實驗流程…………………………………………….14 第三節 HN242配置及….…………………..………………………….14 第四節 高脂飼料配方………………………………………………………..14 第五節 IPGTT 與IPITT…………………………………….………………15 第六節 尿液血液分析 kit………………………..………………………….15 第七節 細胞培養…………………………………………………………….18 第八節 細胞存活率分析…………………………………………………….18 第九節 組織石蠟包埋法…………………………………………………….19 第十節 蘇木精-伊紅染色 (Hematoxylin-Eosin stain)……………………..19 第十一節 Trichrome stain…………………………………………………...20 第十二節 西方墨點法分析……...……………………………………………21 第十三節 電顯包埋切片法……………………………………………………25 第十四節 尿液比重測量………………………………………………………26 第十五節 冷切包埋法……………………………………………………26 第十六節DCFHDA及DHE染色法…………………………………….26 第十七節 自由基測定儀 Chemiluminescence……………………………….27 第十八節 流式細胞儀分析…………………………………………………..28 第十九節 海馬生物代謝儀…………………………………………………..29 第二十節 Glucose(2-DG)/glutamine uptake assay……………………………30 第二十一節 PAS staining kit及計算方式……………………………………….32 第二十二節 小鼠血壓測量法…………………………………………………32 第二十三節 統計分析…………………………………………………..……….33 第三章 實驗結果……………………………………………………………………………………….…………..34 第一節 以高脂飼料餵食C57BL/6小鼠誘發體重增加及糖尿病產生……32 第二節 經組織切片染色證明HN242可以有效預防腎臟損傷及保護腎臟 組織……………………………………………………………………………………………35 第三節 HN242可維持腎絲球過濾膜及腎小管型態…………………………….35 第四節 利用Palmitate acid處理MES13腎間質細胞模擬小鼠高脂 飲食環境以及HN242對於MES13的有效保護濃度……………...36 第五節 HN242可維持和保護腎絲球過濾膜及腎小管正常功能………….36 第六節 高脂飲食及棕櫚酸造成氧化壓力上升使腎絲球細胞受損……...37 第七節 HN242抑制氧化壓力對小鼠腎臟組織及MES13細胞造成的發炎 反應……………………………………….……………………………………………………38 第八節 高脂飲食造成的氧化壓力對腎臟組織及MES13細胞的代謝與粒線體功能影響………………………………………………………………..39 第九節 氧化壓力影響的醣類沉積使腎臟組織及腎臟細胞受損…………..39 第十節 腎臟受損對於血壓的影響……………………………………………………….39 第四章 討論…………………………………………………………………………………………………………41 第一節 簡述……………………………………………………….…41 第二節 高脂飲食與糖尿病…………………………………………..41 第三節 Palmitate acid模擬高脂飲食環境……………………….42 第四節 近代糖尿病腎病變藥物治療與研究……………………..42 第五節 胰島素及升糖素外其他恆定血糖內分泌激素…………………….43 第六節 胰島素治療藥物與胰島素增敏劑……………………………….………43 第七節 糖尿病腎病變……………………………………………………………………..……44 第八節 糖尿病腎病變與氧化壓力之探討………………………..45 第九節 PKC pathway…………………………………………………..46 第十節 終期糖化終產物AGEs與其受體………………………………46 第十一節 Autophagy與糖尿病腎病變…………………………………….47 第十二節 氧化壓力導致發炎反應之路徑………………………………47 第十三節 血壓與糖尿病腎病變…………………………………………..48 第十一節 第二型糖尿病與胰島素阻抗…………………………………….49 第十二節 肥胖與胰島素阻抗………………………………………………..50 第十三節 葡萄糖受體………………………………………………………50 第五章 結論……………………………………………………………………………………………………….….52 第六章 附圖……………………………………………………………………………………………….53 第七章 參考文獻………………………………………………………………………………………..88 第八章 Supplementary figure 附圖……………………………………………………96 | |
| dc.language.iso | zh-TW | |
| dc.subject | 抗氧化 | zh_TW |
| dc.subject | HN242 | zh_TW |
| dc.subject | 高脂飲食 | zh_TW |
| dc.subject | 糖尿病 | zh_TW |
| dc.subject | 腎病變 | zh_TW |
| dc.subject | 腎臟間質細胞 | zh_TW |
| dc.subject | High fat diet | en |
| dc.subject | Anti-oxidant | en |
| dc.subject | MES13 | en |
| dc.subject | Nephropathy | en |
| dc.subject | Diabetes | en |
| dc.subject | HN242 | en |
| dc.title | 植物萃取物HN242對高血糖引起之腎臟病變的預防與保護作用 | zh_TW |
| dc.title | Prevention and protection effects of a plant extract HN242 on hyperglycemia-induced kidney disease | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王淑慧(Shu-Hui Wang),許美鈴,陳瀅,姜至剛 | |
| dc.subject.keyword | HN242,高脂飲食,糖尿病,腎病變,腎臟間質細胞,抗氧化, | zh_TW |
| dc.subject.keyword | HN242,High fat diet,Diabetes,Nephropathy,MES13,Anti-oxidant, | en |
| dc.relation.page | 102 | |
| dc.identifier.doi | 10.6342/NTU201602766 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-17 | |
| 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 |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
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