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標題: | 不同葉酸含量對高油飲食小鼠腎臟的影響 Effects of high-fat diet and folate status on kidney |
作者: | Xiang-Lin Koh 辜祥霖 |
指導教授: | 林璧鳳 |
關鍵字: | 高油誘發肥胖,葉酸缺乏,腎臟纖維化,TGF-β,galectin-3, high-fat-diet induced obesity,folate deficiency,renal fibrosis,TGF-β,galectin-3, |
出版年 : | 2016 |
學位: | 碩士 |
摘要: | 台灣的末期腎臟病發生率自2001年十年以上排名世界之冠,現代化生活的飲食型態趨向於高油低蔬果,是否葉酸營養會影響腎健康議題值得探討。有研究指出人體血液葉酸含量與慢性腎衰竭發生率呈負相關,因此,本研究探討葉酸對高油誘發肥胖小鼠的腎臟之影響。實驗方法先以不同葉酸含量培養小鼠腎間膈細胞株MES-13,測定細胞分泌促發炎細胞激素的含量是否受葉酸缺乏影響,並且分析高油誘發肥胖小鼠的腎臟發炎相關基因表現與葉酸的相關性。進而以實驗動物,分別給C57BL/6J公鼠正常油脂 (NF-f1) 組與不同葉酸含量的高油飲食:葉酸缺乏組(HF-f0)、葉酸1倍組(HF-f1)與葉酸10倍組(HF-f10),分組餵飼48週時給予馬兜鈴酸三週後犧牲,測定血液、脾臟與腎臟發炎細胞激素和促纖維化指標TGF-β與galectin-3、及腎臟組織切片觀察。結果顯示,小鼠腎間膈細胞株MES13在LPS (lipopolysaccharide)刺激下,葉酸缺乏時,顯著分泌較高的IL-6與MCP-1。高油誘發肥胖小鼠之腎臟Il-6基因表現量,也與血液葉酸含量呈負相關 (r=-0.69, p=0.002),顯示葉酸缺乏可能促進腎臟發炎反應。並且,葉酸缺乏的高油肥胖小鼠HF-f0組有顯著較高的發炎性細胞激素例如血清IL-6,以及顯著的促纖維化指標,包括血清和腎臟galectin-3含量、血清與腎臟以及脾臟細胞分泌的TGF-β含量。此外, HF-f0組也有顯著較高的尿蛋白比值、腎病理組織染色的腎絲球面積較大、細胞浸潤較多、以及基底膜增厚的現象。綜合以上結果顯示,葉酸缺乏可能促進高油誘發肥胖小鼠的發炎反應與腎臟纖維化進展。 End-stage renal disease in Taiwan had the highest prevalence in the world for more than ten years since 2001. To study whether the folate status in high-fat diets with low vegetables and fruits intake in industrialized countries, which may be related to kidney disease. It has been reported that there was a negative correlation between human serum folate concentration and chronic kidney failure. This study aimed to investigate the effects of folate deficiency on kidney in high-fat diet mice. First, MES-13 mesangial cells were used to investigate the influence of different folate status on the secretion of pro-inflammatory cytokines in vitro. Also, analysing the correlation between renal gene expression of inflammation-related cytokines and serum folate concentration in high-fat fed mice. Next, C57BL/6 male mice fed with normal-fat diet (NF-f1) and high-fat diet were divided into three groups randomly: no folate (HF-f0) as folate deficient group, 2 mg folate/kg diet as a control group (HF-f1), and 20 mg folate/kg diet as high folate group (HF-f10). Mice were sacrificed at week 51 after giving 3 weeks aristolochic acid in the high-fat diet and analyzed (1) Cytokines from blood, splenocytes, kidney, and (2) TGF-β, galectin-3 from blood, kidney, (3) Histological sections of the kidney. Results indicated that folate deficiency group had higher secretion of IL-6 and MCP-1 in LPS stimulated MES-13. There was a negative correlation between serum folate concentration and renal il-6 mRNA gene expression in 20 weeks high-fat diet mice (r=-0.69, p=0.002). Also, folate deficiency group had higher serum IL-6, galectin-3 in blood and kidney, TGF-β in blood, splenocytes, kidney and had higher urine protein/creatinine ratio, In addition, glomerular sections were expanded, elevated cellular infiltration and glomerular basement membrane expansion in the folate deficiency group. In conclusion, folate deficiency may promote the inflammatory response and renal fibrosis progression. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78136 |
DOI: | 10.6342/NTU201602312 |
全文授權: | 有償授權 |
顯示於系所單位: | 生化科技學系 |
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