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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94011
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dc.contributor.advisor林璧鳳zh_TW
dc.contributor.advisorBi-Fong Linen
dc.contributor.author陳亭語zh_TW
dc.contributor.authorTing-Yu Chenen
dc.date.accessioned2024-08-14T16:14:24Z-
dc.date.available2024-08-15-
dc.date.copyright2024-08-13-
dc.date.issued2024-
dc.date.submitted2024-08-08-
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陳駿威(2023)。葉酸營養狀況對脂質代謝和慢性腎病變的影響之研究。國立臺灣大學生化科技學系暨研究所博士論文
國健署(2018),臺灣國民營養健康狀況變遷調查成果報告(民國102-105年)
國健署(2022),臺灣國民營養健康狀況變遷調查成果報告(民國106-109年)
經濟部統計處(2024),批發、零售及餐飲業營業額統計,餐飲業營業額部分。
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94011-
dc.description.abstract已知高含糖飲料低蔬果攝取的飲食型態,可能導致慢性腎病盛行率上升。近年來,研究指出腺嘌呤可作為誘發小鼠腎損傷的媒介。故本研究以腺嘌呤誘發腎損傷小鼠探討果糖與葉酸對腎功能的影響。首先建立腺嘌呤誘發腎損傷小鼠模式,將28週齡的C57BL/6雄鼠分為 (1)正常飲食組 (Ctrl)、低劑量組 (0.1% ade)以及高劑量組 (0.15% ade),餵飼六週後結果顯示,ade兩組都能顯著增加腎功損傷指標,而0.1% ade組體重下降幅度較低,故選擇0.1% 腺嘌呤進行後續實驗。首先探討果糖與葉酸不足對腎功能的影響,將7週齡的C57BL/6雄鼠分為 (1)正常飲食組 (Ctrl)、(2)高果糖組 (Hfru(ade))、(3)高果糖腺嘌呤組 (Hfru +ade)、和 (4)高果糖缺葉酸腺嘌呤組 (Hfru-f +ade)。小鼠22週齡開始添加0.1% (w/w) 腺嘌呤誘發腎損傷,44週齡犧牲分析腎功能指標。結果顯示,不論高果糖組或腺嘌呤 (+ade) 組的飲水量與血清尿素氮、血清肌酸酐、尿蛋白、腎纖維化區域和免疫細胞浸潤顯著增加,Hfru-f +ade組的尿腎損傷分子-1 (KIM-1)較高。顯示葉酸不足加劇腎損傷。接著,為探討純果糖與葉酸補充對腎功能的影響,8週齡的C57BL/6雄鼠分為 (1)正常飲食組 (Ctrl)、(2)高果糖組 (Hfru)、(3)正常飲食腺嘌呤組 (Ctrl +ade)、(4)高果糖腺嘌呤組 (Hfru +ade)、(5)高果糖低葉酸腺嘌呤組 (Hfru-f +ade)以及 (6)高果糖葉酸補充腺嘌呤組 (Hfru+f10+ade)。小鼠18週齡添加0.1%~0.2% (w/w) 腺嘌呤誘發腎損傷,25週齡時犧牲。結果顯示,高果糖組 (Hfru) 體重與肝脂肪比控制組顯著較高,Hfru-f +ade組腎功能顯著降低,而補充葉酸顯著降低血清肌酸酐。綜上所述,高果糖會增加肝脂肪堆積造成肥胖,葉酸不足加劇腎損傷,葉酸補充能減緩腎臟損傷。zh_TW
dc.description.abstractDietary patterns high in sugary beverages and low in fruits and vegetables have been linked to the increasing prevalence of chronic kidney disease. Recent studies have identified adenine as a mediator that induces kidney injury in mice. This study investigates the effects of fructose and folate on renal function in adenine-induced kidney injury murine model.First, we established a mouse model of adenine-induced kidney injury. 28week-old male C57BL/6 mice were divided into three groups: (1) normal diet (Ctrl), (2) low-dose adenine (0.1% ade), and (3) high-dose adenine (0.15% ade). After 6 weeks, both adenine groups showed significant increases in kidney injury markers, with less weight loss in the 0.1% ade group. Therefore, 0.1% adenine was chosen for subsequent experiments. To explore the effects of fructose and folate deficiency on renal function, 7 week-old male C57BL/6 mice were divided into four groups: (1) normal diet (Ctrl), (2) high fructose (Hfru(ade)), (3) high fructose with adenine (Hfru +ade), and (4) high fructose with folate insufficiency and adenine (Hfru-f +ade). From the age of 22 weeks, the mice were treat with 0.1% (w/w) adenine to induce kidney injury, and were sacrificed at 44 weeks of age for analysis. The results showed that both Hfru and ade groups showed significantly increased water intake, serum urea nitrogen, serum creatinine, urinary protein, renal fibrosis areas, and immune cell infiltration. The Hfru-f +ade group had higher levels of urinary kidney injury molecule-1 (KIM-1), indicating that folate deficiency exacerbates kidney damage. To further investigate the impact of fructose and folate supplementation on renal function, 8 week-old male C57BL/6 mice were divided into six groups: (1) normal diet (Ctrl), (2) high fructose (Hfru), (3) normal diet with adenine (Ctrl +ade), (4) high fructose with adenine (Hfru +ade), (5) high fructose with low folate with adenine (Hfru-f +ade), and (6) high fructose with folate supplementation with adenine (Hfru+f10+ade). From the age of 18 weeks, the mice were treat with 0.1~0.2% (w/w) adenine to induce kidney injury, and were sacrificed at 25 weeks of age for analysis. The results showed that the Hfru group had significantly higher body weight and liver fat compared to the control group. The Hfru-f +ade group exhibited significantly reduced renal function, while Hfru+f10+ade significantly lowered serum creatinine levels.These results demonstrated that high fructose increases liver fat accumulation. Low folate exacerbates kidney damage by increasing fibrosis, while folate supplementation can mitigate kidney injury.en
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dc.description.tableofcontents口試委員審定書 ............................................................................................................... i
謝辭 .................................................................................................................................. ii
摘要 ................................................................................................................................. iii
Abstract............................................................................................................................ iv
目次 ................................................................................................................................. vi
圖次 .................................................................................................................................. x
表次 ................................................................................................................................ xii
第一章 文獻回顧 ......................................................................................... 1
第一節葉酸 .................................................................................................. 1
一、化學結構 .......................................................................................... 1
二、生理生化功能 .................................................................................. 2
三、食物來源與建議攝取量 .................................................................. 3
四、消化吸收與儲存 .............................................................................. 3
六、缺乏症 .............................................................................................. 5
七、葉酸營養狀況 .................................................................................. 7
第二節果糖 .................................................................................................. 8
一、化學結構與來源 .............................................................................. 8
二、生化代謝 .......................................................................................... 8
三、消化吸收 ........................................................................................ 10
四、果糖與疾病 .................................................................................... 10
第三節腺嘌呤 ............................................................................................ 13
一、化學結構與來源 ............................................................................ 13
二、生理功能與代謝機轉 .................................................................... 13
三、腺嘌呤對全身代謝的影響 ............................................................ 15
四、 腺嘌呤對腎臟的影響 .................................................................... 16
五、 腺嘌呤誘發腎病模式 .................................................................... 16
第四節 腎臟疾病 ........................................................................................ 21
一、 腎結石 (kidney stone) ................................................................... 21
二、 急性腎損傷 (Acute kidney injury, AKI) ....................................... 23
三、 慢性腎病變 (chronic kidney disease, CKD) ................................. 24
第五節 研究動機與目的 ............................................................................ 30
第二章 腺嘌呤誘發腎損傷的劑量實驗 ................................................... 32
第一節 前言 ................................................................................................ 32
第二節 材料方法 ........................................................................................ 33
一、 動物飼養 ........................................................................................ 33
二、 血液採集與處理 ............................................................................ 33
三、 尿液採集與處理 ............................................................................ 33
四、 腎功能測定 .................................................................................... 35
五、 腎臟組織切片染色 ........................................................................ 36
六、 統計分析 ........................................................................................ 37
第三節 實驗結果 ........................................................................................ 38
一、 腺嘌呤誘發腎損傷小鼠生長情形 ................................................ 38
二、 小鼠組織器官重量 ........................................................................ 40
二、 腺嘌呤對小鼠腎功能的影響 ........................................................ 41
三、 腺嘌呤對小鼠腎纖維化的影響 .................................................... 42
第四節 討論 ................................................................................................ 43
第三章 果糖與葉酸不足對腺嘌呤誘發腎損傷小鼠腎功能的影響 ...... 46
第一節 前言 ................................................................................................ 46
第二節 材料方法 ........................................................................................ 47
一、 動物飼養 ........................................................................................ 47
二、 血液採集與處理 ............................................................................ 47
三、 尿液採集與處理 ............................................................................ 47
四、 血清葉酸濃度測定 ........................................................................ 49
五、 腎功能測定 .................................................................................... 51
六、 腎臟組織切片染色 ........................................................................ 52
七、 統計分析 ........................................................................................ 52
第三節 實驗結果 ........................................................................................ 53
一、 小鼠生長情形 ................................................................................ 53
二、 小鼠組織器官重量 ........................................................................ 58
三、 腎功能指標 .................................................................................... 59
四、 腎損傷小鼠腎臟組織病理變化和纖維化的影響 ........................ 60
第四節 討論 ................................................................................................ 62
一、 高油高果糖與葉酸對小鼠體重的影響 ........................................ 62
二、 腺嘌呤對小鼠體重與腎功能的影響 ............................................ 62
三、 腺嘌呤誘發之腎損傷無法回復 .................................................... 63
四、 果糖與腺嘌呤對小鼠熱量攝取與血糖的影響 ............................ 63
五、 葉酸缺乏使小鼠攝食量與體重減輕 ............................................ 64
六、 腺嘌呤餵飼增加飲水量與尿量 .................................................... 64
七、 果糖與葉酸不足對腎臟外觀的影響 ............................................ 64
八、 果糖與葉酸不足對腎功能指標的影響 ........................................ 65
九、 果糖與葉酸不足加劇組織病理變化和纖維化 ............................ 66
第四章 果糖與葉酸補充對腺嘌呤誘發腎損傷小鼠的影響 .................. 68
第一節 前言 ................................................................................................ 68
第二節 材料方法 ........................................................................................ 69
一、 動物飼養 ........................................................................................ 69
二、 血液採集與處理 ............................................................................ 69
三、 尿液採集與處理 ............................................................................ 69
四、 血清葉酸濃度測定 ........................................................................ 71
五、 肝功能測定 .................................................................................... 71
六、 肝臟脂肪測定 ................................................................................ 71
七、 腎功能測定 .................................................................................... 72
八、 腎臟組織切片染色 ........................................................................ 73
九、 腎臟mRNA 表現量分析 ............................................................... 73
十、 統計分析 ........................................................................................ 76
第三節 實驗結果 ........................................................................................ 77
一、 小鼠生長情形 ................................................................................ 77
二、 小鼠組織器官重量 ........................................................................ 80
三、 小鼠體內葉酸濃度 ........................................................................ 81
四、 果糖、葉酸與腺嘌呤對小鼠血糖的影響 .................................... 82
五、 果糖、葉酸與腺嘌呤對小鼠消化道的影響 ................................ 83
六、 果糖、葉酸與腺嘌呤對小鼠肝功能的影響 ................................ 84
七、 果糖、葉酸與腺嘌呤對小鼠脂肪堆積的影響 ............................ 85
八、 果糖、葉酸與腺嘌呤對小鼠腎臟的影響 .................................... 87
第四節 討論 ................................................................................................ 92
一、 果糖與葉酸對小鼠生長情形的影響 ............................................ 92
二、 葉酸與腺嘌呤對小鼠器官重量的影響 ........................................ 92
三、 飲食葉酸對小鼠體內葉酸濃度的影響 ........................................ 93
四、 果糖對小鼠禁食血糖與尿糖的影響 ............................................ 93
五、 果糖、葉酸與腺嘌呤對肝功能的影響 ........................................ 94
六、 果糖增加小鼠肝臟脂肪堆積 ........................................................ 94
七、 果糖與葉酸對腎功能與腎纖維化的影響 .................................... 95
第五章 綜合討論與結論 ........................................................................... 96
第一節 綜合討論 ........................................................................................ 96
一、 葉酸與腺嘌呤代謝相互作用 ........................................................ 96
二、 飲食葉酸對體內葉酸含量的影響 ................................................ 97
三、 飲食因子影響腺嘌呤誘發腎損傷可能的原因 ............................ 97
第二節 結論 ................................................................................................ 99
參考文獻 ................................................................................................... 101
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dc.language.isozh_TW-
dc.subject葉酸zh_TW
dc.subject果糖zh_TW
dc.subject纖維化zh_TW
dc.subject腎功能zh_TW
dc.subject腺嘌呤zh_TW
dc.subjectadenineen
dc.subjectrenal functionen
dc.subjectfibrosisen
dc.subjectfolateen
dc.subjectfructoseen
dc.title果糖與葉酸對腺嘌呤誘發腎損傷小鼠腎功能的影響zh_TW
dc.titleEffects of fructose and folate on renal function in adenine-induced kidney injury murine modelen
dc.typeThesis-
dc.date.schoolyear112-2-
dc.description.degree碩士-
dc.contributor.oralexamcommittee許瑞芬;江孟燦;洪永瀚;謝佳倩zh_TW
dc.contributor.oralexamcommitteeRwei-Fen Syu Huang;Meng-Tsan Chiang;Yong-Han Hong;Chia-Chien Hsiehen
dc.subject.keyword果糖,葉酸,腺嘌呤,腎功能,纖維化,zh_TW
dc.subject.keywordfructose,folate,adenine,renal function,fibrosis,en
dc.relation.page111-
dc.identifier.doi10.6342/NTU202403133-
dc.rights.note同意授權(全球公開)-
dc.date.accepted2024-08-10-
dc.contributor.author-college生命科學院-
dc.contributor.author-dept生化科技學系-
顯示於系所單位:生化科技學系

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