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系統識別號 U0026-0812200914255758
論文名稱(中文) 老人衰弱與氧化壓力之相關性研究
論文名稱(英文) Frailty and Oxidative Stress in the Elderly
校院名稱 成功大學
系所名稱(中) 臨床醫學研究所
系所名稱(英) Institute of Clinical Medicine
學年度 96
學期 2
出版年 97
研究生(中文) 吳易謙
研究生(英文) I-chien Wu
電子信箱 s9695109@mail.ncku.edu.tw
學號 S9695109
學位類別 碩士
語文別 英文
論文頁數 70頁
口試委員 指導教授-郭柏秀
指導教授-謝淑珠
指導教授-林錫璋
口試委員-蔡曜聲
中文關鍵字 白蛋白  腰臀比  氧化壓力  老化  C-反應蛋白  發炎  8-羥基脫氧鳥苷  衰弱  生物指標 
英文關鍵字 DNA/metabolism  biological markers/blood  DNA damage/physiology  waist-hip ratio  aging  frail elderly  inflammation  cross-sectional studies  Aged  humans  C-reactive protein  walking/physiology  hand strength  oxidative stress 
學科別分類
中文摘要 背景:衰弱(frail)的老人因為肌肉過度萎縮併脂肪組織堆積以及全身的發炎反應,導致活動力下降、體重減輕,且有極高的罹病率及死亡率。體內氧化壓力隨者年齡增加,且氧化壓力與肌肉萎縮、肥胖及發炎反應有密切相關。因此本研究欲探討體內氧化壓力與衰弱之關係。
目標:探討衰弱的老人血中是否有較高濃度的8-羥基脫氧鳥苷(8-OHdG)以及較低的抗氧化能力。
研究方法:我們進行一觀察性質的橫斷面分析研究。研究對象為社區及研究期間至本院老年科門診就診且大於65歲的患者,但排除罹患癌症、巴金森氏症或中風之老人。對於研究對象我們藉評估手部握力、體重變化、行走速度、耗盡與否及身體活動下降程度來評估衰弱狀態,同時抽血測量血清8-羥基脫氧鳥苷濃度及血清抗氧化能力。我們亦測量代謝指標(身體質量指數、腰臀比、血脂肪、空腹血糖和白蛋白)及發炎指標[高感度C-反應蛋白(hs-CRP)]。不同衰弱程度的受試者在各個變項上的差異以One-way ANOVA及chi-square test for trend分析。兩變項之間的相關性與多變項之間的相關性則分別以Spearman correlations及 ordinal regression分析。Receiver operating characteristic (ROC) 曲線則用以評估整合性生理模型在篩檢衰弱老人上的準確性(accuracy)。
結果:總共有90位研究對象,平均年齡77歲。21位 (23.3%)為衰弱老人,13位 (14.4%)為健康老人,其餘56位 (62.2%)屬衰弱前期。衰弱老人與衰弱前期及健康老人相較,有較高濃度的血清8-羥基脫氧鳥苷 (3.0±1.5 vs. 2.8±1.9 and 1.4±1.5 ng/mL)、較高濃度的血清高感度C-反應蛋白(6.5±8.7 vs. 4.9±9.1 and 1.7±1.0 mg/L)、較低濃度的血清白蛋白 (4.1±0.4 vs. 4.4±0.4, 4.6±0.2 g/dL)以及較高的腰臀比 (0.96±0.11 vs. 0.91±0.07, 0.89±0.05) (所有皆p< 0.05)。整合血清8-羥基脫氧鳥苷、血清高感度C-反應蛋白以及血清白蛋白的生理模型可以準確地區分健康與衰弱的老人(敏感度為0.96,特異度為0.75)。經過迴歸分析後,高濃度的血清8-羥基脫氧鳥苷與衰弱之間呈現獨立的相關。
結論: 血清8-羥基脫氧鳥苷的濃度與老人衰弱有獨立的相關性。因此,在老人衰弱的致病機轉中,氧化壓力應扮演一獨立且重要的角色。
英文摘要 Background: Frail elders have high morbidity and mortality, and are characterized by loss of skeletal muscle mass, increased and redistributed fat mass as well as systemic inflammation. Oxidative stress increases with age, and is closely related to muscle mass loss, obesity and systemic inflammation. We hypothesized that frail elders had higher oxidative stress as compared with non-frail elders.
Objectives: To determine whether serum 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels and serum total antioxidant capacity (TAC) correlates with frailty status of elders.
Method: A cross-sectional study of community-dwelling adults and geriatric clinic patients at the age of 65 or older without malignancy, stroke and Parkinson’s disease was performed. Frailty status was classified as frail, prefrail and robust, and was determined by handgrip strength, weight changes, walking speed, exhaustion, and activity level. Blood was drawn to measure serum 8-OHdG level and TAC. Metabolic markers (body mass index, waist-hip ratio, blood lipid, glucose and albumin) and inflammatory markers (hs-CRP) were also measured. Differences between groups were analyzed with the one-way ANOVA and chi-square test for trend. Spearman correlations were used to assess bivariate associations while multivariate associations were assessed with ordinal regression. Receiver operating characteristic (ROC) curve was used to examine the accuracy of proposed physiologic model.
Results: A total of 90 subjects with mean age of 77 years were recruited. 21 subjects (23.3%) were identified as frail, while 56 subjects (62.2%) were prefrail and 13 subjects (14.4%) were robust. Frail vs. prefrail and robust subjects had higher serum 8-OHdG levels (3.0±1.5 vs. 2.8±1.9 and 1.4 ±1.5 ng/mL), higher serum hs-CRP (6.5±8.7 vs. 4.9±9.1 and 1.7±1.0 mg/L), lower serum albumin (4.1±0.4 vs. 4.4±0.4 and 4.6±0.2 g/dL) and higher waist-hip ratio (0.96±0.11 vs. 0.91±0.07 and 0.89±0.05) (p<0.05 for all). Model integrating serum 8-OHdG, hsCRP and albumin levels were accurate in identifying frail or prefrail elders with sensitivity of 0.96 and specificity of 0.75. In regression analysis, high serum 8-OHdG levels was significantly associated with frailty after adjusting for age, gender, diabetes, hypertension, smoking, blood glucose, lipid levels, waist-hip ratio, serum albumin and hs-CRP levels.
Conclusion: Increased serum 8-OHdG level was independently associated with frailty. These findings support the hypothesis that increased oxidative stress plays important role in frailty.
論文目次 Abstract in Chinese-------------------------------------2
Abstract in English-------------------------------------4
Acknowledgments-----------------------------------------6
Introduction-------------------------------------------11
Specific Aims------------------------------------------15
Significance-------------------------------------------16
Methods------------------------------------------------17
Participants-------------------------------------------17
Assessing frailty status of subjects-------------------17
Central obesity, glucose, lipid and protein metabolism-20
Assessing systemic inflammation------------------------20
Measuring oxidative DNA damage-------------------------21
Determining serum total antioxidant capacity-----------21
Confounders--------------------------------------------22
Ethical issues-----------------------------------------22
Statistical analysis-----------------------------------22
Results------------------------------------------------24
Aim1. To determine whether frail subjects have more centrally-distributed fat with altered glucose, lipid and protein metabolism -------------------------------------26
Aim2. To determine whether frail subjects have elevated systemic inflammation----------------------------------27
Aim3. To determine whether frail subjects have higher serum level of 8-OHdG and less serum total antioxidant capacity-----------------------------------------------28
Aim4. To determine whether a model integrating oxidative stress, inflammation and protein catabolism could accurately identify frail elders-----------------------29

Discussion---------------------------------------------30
Oxidative DNA damage and frailty-----------------------30
Inflammation and frailty-------------------------------34
Metabolism and frailty---------------------------------35
Integrative physiologic model of frailty---------------37
Limitations--------------------------------------------38
Conclusion---------------------------------------------39
Tables and Figure Legends------------------------------40
References---------------------------------------------60
Appendix-----------------------------------------------66
1------------------------------------------------------66
2------------------------------------------------------67
3------------------------------------------------------70
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