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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 程蘊菁(Yen-Ching Chen) | |
dc.contributor.author | Ying-Shu You | en |
dc.contributor.author | 尤瀅淑 | zh_TW |
dc.date.accessioned | 2021-05-17T09:14:19Z | - |
dc.date.available | 2017-09-17 | |
dc.date.available | 2021-05-17T09:14:19Z | - |
dc.date.copyright | 2012-09-17 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-08-16 | |
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Martin A, de Vittoris R, David V, Moraes R, Begeot M, Lafage-Proust MH, Alexandre C, Vico L, Thomas T. Leptin modulates both resorption and formation while preventing disuse-induced bone loss in tail-suspended female rats. Endocrinology 2005;146:3652-9. 45. Adami S, Braga V, Zamboni M, Gatti D, Rossini M, Bakri J, Battaglia E. Relationship between lipids and bone mass in 2 cohorts of healthy women and men. Calcif Tissue Int 2004;74:136-42. 46. Brownbill RA, Ilich JZ. Lipid profile and bone paradox: higher serum lipids are associated with higher bone mineral density in postmenopausal women. J Womens Health (Larchmt) 2006;15:261-70. 47. Yamaguchi T, Sugimoto T, Yano S, Yamauchi M, Sowa H, Chen Q, Chihara K. Plasma lipids and osteoporosis in postmenopausal women. Endocr J 2002;49:211-7. 48. Cui LH, Shin MH, Chung EK, Lee YH, Kweon SS, Park KS, Choi JS. Association between bone mineral densities and serum lipid profiles of pre- and post-menopausal rural women in South Korea. Osteoporos Int 2005;16:1975-81. 49. Orozco P. Atherogenic lipid profile and elevated lipoprotein (a) are associated with lower bone mineral density in early postmenopausal overweight women. Eur J Epidemiol 2004;19:1105-12. 50. Serre CM, Farlay D, Delmas PD, Chenu C. Evidence for a dense and intimate innervation of the bone tissue, including glutamate-containing fibers. Bone 1999;25:623-9. 51. Skerry TM, Genever PG. Glutamate signalling in non-neuronal tissues. Trends Pharmacol Sci 2001;22:174-81. 52. Chenu C, Serre CM, Raynal C, Burt-Pichat B, Delmas PD. Glutamate receptors are expressed by bone cells and are involved in bone resorption. Bone 1998;22:295-9. 53. Behl C, Skutella T, Lezoualc'h F, Post A, Widmann M, Newton CJ, Holsboer F. Neuroprotection against oxidative stress by estrogens: structure-activity relationship. Mol Pharmacol 1997;51:535-41. 54. Singer CA, Figueroa-Masot XA, Batchelor RH, Dorsa DM. The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. J Neurosci 1999;19:2455-63. 55. Zhu X, Liu X, He P, Cao B, Lv Y, Zhang W, Ni X. Metabolomics in serum of ovariectomised rats and those exposed to 17beta-oestradiol and genistein. Gynecol Endocrinol 2010;26:760-7. 56. Ma B, Zhang Q, Wang GJ, A JY, Wu D, Liu Y, Cao B, Liu LS, Hu YY, Wang YL, Zheng YY. GC-TOF/MS-based metabolomic profiling of estrogen deficiency-induced obesity in ovariectomized rats. Acta Pharmacol Sin 2011;32:270-8. 57. Rapuri PB, Kinyamu HK, Gallagher JC, Haynatzka V. Seasonal changes in calciotropic hormones, bone markers, and bone mineral density in elderly women. J Clin Endocrinol Metab 2002;87:2024-32. 58. Frankenfeld CL, McTiernan A, Thomas WK, LaCroix K, McVarish L, Holt VL, Schwartz SM, Lampe JW. Postmenopausal bone mineral density in relation to soy isoflavone-metabolizing phenotypes. Maturitas 2006;53:315-24. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/6515 | - |
dc.description.abstract | 背景:近期已有研究指出骨質疏鬆症與體內不斷循環的特定代謝物具有相關;然
而,若單靠過去研究所探討的少數幾項代謝物,很難對此複雜的致病機轉做詳確 的解釋。如今,代謝體學方法可全面性的檢視人體中代謝情形和潛在的臨床意義。 截至目前為止,未有研究加以驗證人體中代謝體特徵和骨質密度之間的相關。 方法:本研究橫斷式研究設計,自 2009 到 2010 年間招募 610 位年齡介於 40 至55 歲之間在台北美兆健康檢查中心參加健康檢查的台灣女性。使用雙能量放射線儀測量隻腰椎骨質密度,以骨質密度值的高低排序後研究族群依人數均分為三等份,定義骨質密度最高的第二和第三分群為「高骨質密度」組別,而最低的第 一群為「低骨質密度」組別。而血漿代謝體特徵資料是透過核磁共振氫譜實驗分 析所收集而成。運用無監督的主成分分析、監督的偏最小二乘法判別分析法及邏 輯斯迴歸模式,來分析代謝體特徵與骨質密度的相關。 結果:研究結果顯示,無監督的主成分分析的分數散佈圖無法完善地分離高低骨 質密度的組別;監督的偏最小二乘法判別分析法亦沒有能力區別高低骨質密度的 組別。根據停經狀態加以分層之後,可透過偏最小二乘法判別分析法於停經婦女 群體觀察到其代謝體特徵與高低骨質密度顯著的差異(R2= 0.12;Q2=0.04; P permutation =0.03)。此外,在停經婦女身上,會隨著glutamine的濃度升高,使得低骨質密度的風險增加;同時,低骨質密度也與lactate、acetone、lipid 和 very low density lipoprotein濃度降低具有相關。 結論:這是第一篇研究透過核磁共振氫譜實驗所建立的代謝體學與骨質密度之 研究,我們成功地於停經婦女群體辨識出一群代謝物和低骨質密度具有關聯。其 中,特別是glutamine的濃度升高會增加低骨質密度發生的風險,可能會因此導致骨骼流失。 | zh_TW |
dc.description.abstract | Background. Osteoporosis has been related to the alteration of specific circulating metabolites previously. However, studies with few metabolites may have difficulty to explain the pathogenesis of this complex syndrome. Metabolome provide an overview of the metabolism status in human body and potential clinical implication. Up to date,no study has investigated the association between metabolome and bone mineral density (BMD).
Methods. This is a cross-sectional study. A total of 610 healthy Taiwanese women aged 40 to 55 were recruited from MJ Health Screening Center between 2009 and 2010. High and low bone mineral density (BMD) was defined as the 2nd plus 3rd tertiles and the 1st tertile of BMD, respectively. The plasma metabolome were evaluated by 1H-nuclear magnetic resonance spectroscopy. Principal components analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and logistic regression model were used to assess the association between metabolomeand BMD. Results. The unsupervised PCA showed no visual separation between low and high BMD levels; the supervised PLS-DA model was also unable to distinguish high and low BMD groups. After stratification by menopausal status, high and low BMD groups can be differentiated in post-menopausal women using PLS-DA (R2= 0.12;Q2=0.04; P permutation =0.03). In addition, elevated level of glutamine was associated with the risk of low BMD among postmenopausal women; while low BMD is characterized by decreased levels of lactate,acetone, lipid, and very low density lipoprotein in the same sub-population. Conclusion. This is the first study using 1H NMR-based metabolomic approach and successfully identified a group of metabolites representative for postmenopausal women with low BMD. Especially, elevated level of glutamine may lead to bone loss via increased risk of low BMD. | en |
dc.description.provenance | Made available in DSpace on 2021-05-17T09:14:19Z (GMT). No. of bitstreams: 1 ntu-101-R99849016-1.pdf: 2123835 bytes, checksum: 56691b27ec99e9a92cc242e8f243c493 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 審訂書.....................................................i
誌謝......................................................ii 摘要.....................................................iii Abstract..................................................v 圖目錄..................................................viii 表目錄 ...................................................ix Chapter 1. Introduction...................................1 1.1 Importance of Osteoporosis ...........................1 1.2 Bone-Related Proteins and Metabolites.................2 1.3 NMR-based Metabolome..................................2 1.4 Aims..................................................3 Chapter 2. Materials and Methods..........................5 2.1 Study Population......................................5 2.2 Measurement of Bone Mineral Density...................6 2.2 Sample Collection and Preparation.....................6 2.3 1D 1H NMR Spectroscopy................................6 2.4 NMR Spectral Pre-Processing...........................7 2.5 Statistical Analyses..................................8 Chapter 3. Results.......................................11 3.1 Characteristics of the Study Population..............11 3.2 Metabolome of the BMD Levels.........................11 3.3 Candidate Metabolites and the Risk of Low BMD........12 Chapter 4. Discussion....................................15 4.1 Main findings........................................15 4.2 Evidences of Metabolites and Bone Metabolism.........15 4.3 Strengths and limitations............................17 4.4 Conclusions..........................................19 References...............................................20 Figure 1. Flowchart of participant recruitment...........30 Figure 2. The tertiles of bone mineral density...........31 Figure 3. PCA score plots from the analysis of CPMG NMR spectra using women plasma samples.......................32 Figure 4. PLS-DA score plots from the analysis of CPMG NMR spectra using women plasma samples.......................33 Figure 5. Receiver operating characteristic curves of comparing models for classification of high and low BMD..34 Figure 6. Acetone distribution by fasting glucose level..35 Figure 7. Postulated mechanism relates important metabolites with bone mineral density among postmenopausal women.....36 Table 1. Characteristics of the study population..........37 Table 2. The PLS-DA parameters and permutation test for differentiating high and low BMD levels..........38 Table 3. The change of plasma metabolites in postmenopausal women to distinguish high and low BMD............39 Table 4. Association between plasma metabolites and bone mineral density (T1 vs. T2+T3)............................40 Table 5. Association between plasma metabolites and bone mineral density stratified by menopausal status (T1 vs. T2+ T3)........................41 Table 6. Receiver operating characteristic contrast tests of pairwise comparison between different models to classify high and low BMD..............................42 Table 7. Model comparisons for the association between plasma metabolites and bone mineral density (T1 vs. T2+T3)....................43 | |
dc.language.iso | en | |
dc.title | 應用核磁共振氫譜技術探討台灣女性代謝體特徵與低骨質密度之關聯研究 | zh_TW |
dc.title | Association of Metabolome with Low Bone Mineral Density in Taiwanese Women Revealed
by 1H NMR Spectroscopy | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 林靖愉(Ching-Yu Lin) | |
dc.contributor.oralexamcommittee | 蔡克嵩(Keh-Sung Tsai),丘政民(Jeng-Min Chiou) | |
dc.subject.keyword | 代謝體特徵,代謝體學,核磁共振氫譜,骨質疏鬆症,停經,女性, | zh_TW |
dc.subject.keyword | metabolomem,metabolic profiles,metabolomics,metabonomics,nuclear magnetic resonance,NMR,bone mineral density,osteoporosis,menopause,women, | en |
dc.relation.page | 43 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2012-08-16 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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