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研究生:陳嗣民
研究生(外文):Szu-Ming Chen
論文名稱:阿滋海默症血液流變學的研究
論文名稱(外文):Hemrheological changes in patients with Alzheimer''s disease
指導教授:劉得任劉得任引用關係
指導教授(外文):Der-Zen Liu
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:生物醫學材料研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2003
畢業學年度:91
語文別:中文
論文頁數:1
中文關鍵詞:阿滋海默症血液流變學紅血球變形度
外文關鍵詞:Alzheimer''''s diseaseHemorheologyErythrocyte deformability
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血液流變學的研究在臨床醫學應用之發展上具有舉足輕重的影響。近年來阿滋海默症病患體內微循環障礙的病理徵象,漸為臨床醫師所重視。本研究主要以血液流變學(Hemorheology)模式評估阿滋海默症(Alzheimer’s disease)老人各項血液流變參數的異常,並討論血液流變參數異常的機制及其對於阿滋海默症老人體內微循環的影響。
研究對象以 6位阿滋海默症老人為實驗組及10位年齡與實驗組相近的正常老人為對照組。兩組受測者以簡易智能狀態測驗(MMSE ; Minimurn Mental State Examination)以評估患者認知功能。經空腹採血進行血液各項生化、血球及血液流變參數檢測。分別於低、中及高剪切率下檢測全血黏度(Whole Blood Viscosity),震盪流中檢測黏彈性(Blood Viscoelasticity),低剪切率下測定紅血球聚集度(Erythrocyte Aggregation),高剪切率下檢測紅血球變形度(Erythrocyte Deformability)及血漿黏度(Plasma Viscosity),及利用Dintenfass所提之公式{Tk= [(ηr0.4-1)/ηr0.4 ] / Hct}計算出紅血球內黏度(Tk Level )。
實驗結果顯示,阿滋海默症老人血液流變各項參數,從巨觀之血液黏度至微觀之紅血球變形度皆顯著異常於正常老人。其中阿滋海默症老人之血液黏度、血漿黏度、血漿纖維蛋白原、血液黏彈性及紅血球聚集度皆明顯高於正常老人,而紅血球變形度則明顯低於正常老人。然而紅血球容積比與紅血球內黏度並無明顯差異。而引起阿滋海默症老人血液中紅血球於低剪切率下表現出高聚集性,使血液黏度增高,其主因為血漿中纖維蛋白原增高。於高剪切率下表現出低變形度,使血液黏度增加則主因於紅血球膜性質的改變之故。
Hemorheological studies were very important in the clinical development. Recently,microvascular abnormalities in Alzheimer’s disease is under intensive investigated.This study to evaluate the changes in hemorheological indexes for patients with Alzheimer’s disease and to discuss the mechanism of these changes and the effects in patients with Alzheimer’s disease.
Six elderly patients with Alzheimer’s disease and ten age-matched healthy subjects were included by evaluating the cognitive function of the Minimum Mental State Examination test (MMSE) . Fasting blood samples were collected to measure the biochemistries, complete blood counts and hemorheological indexes. Whole blood viscosity was measured in low, middle and high shear rate. Blood viscoelasticity was measured in oscillated model, Moreover,erythrocyte aggregation was measured in low shear rate.And plasma viscosity and erythrocyte deformability were measured in high shear. “Tk”level was calculated according to the equation {Tk= [(ηr0.4-1)/ηr0.4 ] / Hct } of Dintenfass.
The result revealed that there were significant different in all hemorheological indexes between Alzheimer’s disease group and control group except Hct and Tk level. Whole blood viscosity, plasma viscosity, viscoelasticity, plasma fibrinogen and erythrocyte aggregation of patients with Alzheimer’s disease group were significant higher than those of normal control group.Erythrocyte deformability of patients with Alzheimer’s disease was significant lower than healthy subjects. The increased erythrocyte aggregation duing low shear rate may due to the increased fibrinogen concentration.The decreased erythrocyte de- formability during high shear rate may result from membrane modification of erythrocyte.
目 錄
謝 誌……………………………………………………………………一
中 文 摘 要……………………………………………………………二
英 文 摘 要……………………………………………………………三
目 錄…………………………………………………………………....四
圖 表 索 引………………………………………………...………….七
第 壹 章 緒論………………………………………………………....1
§ 1 — 1 阿滋海默症的發生……………………………………..……..3
1-1-1 阿滋海默症之病理進展………………………………….…...5
1-1-2 阿滋海默症臨床上異常的表現…………………….………..8
§ 1 — 2 文獻回顧與研究目的………………………………………...10
§ 1 — 3 血液流變學參數……………………………………………...14
一. 黏度………………………………………………………………....14
二. 血漿黏度………………………………………………………. …..16
三. 血液黏度…………………………………………………………....16
四. 物體黏彈性及黏彈流體之介紹…………………………………....19
五. 血液的黏彈流體特性及其影響因素……………………………....19
六. 紅血球變形與量測原理…………………………………………....22
七. 紅血球聚集性與量測原理………………………………………....25
§ 1 — 4 紅血球的生化結構………………………………………..….28
(一). 紅血球膜之組成及結構………….……………………………....28
(二). 紅血球的內成分…………………..……………………………...34
(三). 紅血球的形狀和生化基礎…………………..…………………...36
§ 1 — 5 類澱粉蛋白(β-amyloid protein)的介紹及其臨床意義……...38
一. 類澱粉蛋白的來源………………………………………………...38
二. 類澱粉蛋白的作用………………………………………………...40
第貳章 實驗設備與方法……………………………………………..43
§ 2 — 1 實驗設備……………………………………………………..43
一. 黏度計……………………………………………43
二. 自動水浴溫度控制器……………………………52
三. 自動血球計數分析儀……………………………52
四. 離心機……………………………………………53
五. 紅血球變形及聚集測試儀………………………54
六. 血清生化分析儀………………………………….60
七. 比濁法…………………………………………….60
§ 2 — 2 實驗方法與步驟………………………………..…………...61
§ 2 — 3 實驗流程圖…………………………...……………………..69
第參章 結果…………………………………………………………..70
第肆章 .討論………………………………………………………….77
第伍章 結論與未來展望……………………………………………..85
參考資料………………………………………………………………..88附錄 : 實驗數據………………………………………………………….
圖 表 索 引
圖 1 — 1 : 腦部在早期阿滋海默症受到侵襲的部位…………………...6
圖 1 — 2 : 腦萎縮與阿滋海默症…………………………………….…..7
圖 1 — 3 - a : 阿滋海默症老人腦部微血管之側觀……………………14
圖 1—3—b: 正常老人(A)及阿滋海默症老人(B)腦部微血管之cell free layer與神經元(neuron)間營養物質輸送示意圖….14
圖 1 — 4 : 紅血球膜及骨架之分子模型………………………………32
圖 1 — 5 : β-amyloid(Aβ) plaque的由來……………………………43
圖 2 — 1 : Rotational rheometer RS-I 黏度計之外觀圖………………....48
圖 2 — 2 : 2˚ 之double cone/plate 之 sensor圖……………………..…..49
圖 2 — 3 : Hct = 40% 的血液於不同剪切率下的黏度值(RS-I量測, 操作溫度37˚C , shear rate : 500 ~ 1 )……………...50
圖 2 — 4: Hct = 40% 的血液於固定形變(5%) , 不同頻率(0.2 ~ 5.0 Hz)下之黏彈性參數值(RS-I量測, 操作溫度37˚C )………….…51
圖 2 — 5: 血漿於37˚C , shear rate : 500 下之黏度值…………….52
圖 2 — 6: LG-B-190 Ektacytometer 紅血球變形.聚集分析儀之外觀圖……………………………………………………………...56
圖 2 — 7: LG-B-190 Ektacytometer 紅血球變形.聚集分析儀之升降頭角度范圍顯示及檢體置放旋轉盤板之側觀圖………………...57
圖 2 — 8: LG-B-190 Ektacytometer 紅血球變形.聚集分析儀之升降頭近觀圖…………………………………………………………...58
圖 2 — 9: LG-B-190 Ektacytometer 紅血球變形.聚集分析儀之雷射激光源與檢體置放區顯示圖……………………………………………….59
圖 2- 10: LG-B-190 Ektacytometer 紅血球變形.聚集分析儀之sensor
圖………………………………………………………………………..60
圖 2-11: 紅血球變形測試圖…………………………………………..65
圖 2-12: 紅血球聚集曲線圖…………………………………………..67
表 3 — 1: 阿滋海默症老人與正常老人之臨床生化特性…………….74
表 3 — 2: 阿滋海默症老人與正常老人之血液常規參數…………….75
表 3 — 3: 阿滋海默症老人與正常老人之血液流變參數…………….76
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