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研究生:黃佳雯
研究生(外文):Chia-Wen Huang
論文名稱:異常血液流變T3鼠之腦部記憶行為模式之探討
論文名稱(外文):The study of the animal behavior of T3 rats with abnomal hemorheology
指導教授:方旭偉方旭偉引用關係
口試委員:黃義侑鍾次文
口試日期:2008-06-26
學位類別:碩士
校院名稱:國立臺北科技大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:74
中文關鍵詞:三碘甲狀腺素纖維蛋白原血液流變全血黏度記憶
外文關鍵詞:TriiodothyronineFibrinogenHemorheologicalWhole blood viscosityMemory
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甲狀腺是人體重要的內分泌器官之一,其所分泌的甲狀腺素(Triiodothyronine,T3) 主要功能為調控細胞生長、促進新陳代謝、維持生長與發育的重要因子。反之,過量的T3確會使血液中纖維蛋白原(fibrinogen)上升,導致紅血球的聚集度增加,進而提高血液的黏度,造成血液流變異常。
腦部缺血,會使大鼠腦組織受到氧化傷害,並使得海馬迴(Hippocampus)中麩胱甘肽(glutathione, GSH ) 的含量減少,脂質過氧化的產物—丙二醛(malondial dehyde, MDA)大量產生,神經細胞受到損害,進一步造成水迷宮學習操作能力之障礙。因此,本實驗試著使用T3誘發高纖維蛋白鼠以評估大鼠所誘發之異常血液流變對其腦部認知行為之影響。動物使用8周齡之Sprague-Dawley雄性大白鼠(SD Rats),以口服途徑給予T3(10 μg/100g BW/ day)連續20天,待大鼠產生高纖維蛋以及異常血液流變現象,再與以進行水迷津以及放射狀八爪迷宮的行為測試,以評估高纖維蛋所產生異常血液流變之大鼠,對腦部學習記憶的行為模式之影響。
實驗結果顯示,以T3誘發之甲狀腺亢進之大鼠其血液流變之參數無論是在全血黏度、紅血球聚集度以及血液中纖維蛋白原值,皆比正常之大鼠高;而大鼠之頸動脈在相位對比磁振造影(phase-contrast MRI)之觀測下,亦顯示甲狀腺亢進之大鼠,其頸動脈(carotid artery)之血流速率比控制組大鼠之頸動脈血流速率較慢。此外,我們實驗結果也發現在甲狀腺亢進大鼠之腦組織—海馬迴產生較大量之丙二醛,同時相對於正常之大鼠,腦組織中抗氧化之分子麩胱甘肽會大量的減少。最後,在動物迷宮的行為測試中也得知:甲狀腺亢進所引發之血液流變異常之大鼠,其學習能力較正常之大鼠較差。
  綜合以上發現,利用T3誘發異常血液流變參數之大鼠,由於其血液流動異常將可能導致腦部發生氧化損傷以及海馬迴中丙二醛大量產生、麩胱甘肽的含量減少,進而造成水迷宮空間記憶以及放射狀八爪迷宮的行為學習操作能力之障礙。
Thyroid gland is one of the major endocrine organs in our body. It secretes thyroxine hormone, triiodothyronine (T3) which is a vital factor to our body metabolism, growth, development and differentiation processes. Otherwise, excessive T3 will raise the fibrinogen in the blood certainly leading to the erythrocyte aggregation increasingly, and the whole blood viscosity will enhance, creating the anomaly in hemorheological.
Cerebral ischemia will cause the oxidative damage of the brain tissue, hippocampus, including glutathione depletion and malondial dehyde production, and the neurons will damage, carry out an impaired spatial performance and a barrier for memory study processes observation in Morris water maze and eight-arm radial maze of rats. Therefore, in order to assess the influence of behavioral cognition of its brain, our experiment tries to use T3 to induce the rats with high fibrinogen levels in their blood, which has an anomaly in hemorheological. The male Sprague-Dawley rats of 8 weeks old are used to be as experimental animals, and induce rats with high fibrinogen in their blood, and those rats have anomalies in hemorheological by oral administration of T3 (10 μg/100g BW/ day) for 20 days, in order to estimate the influence on behavioral cognition of rats which have high fibrinogen levels in blood and bring about anomalies in hemorheological, then carrying on behavioral tests by water maze and eight-arm radial maze study.
The experimental result shows that the hemorheological parameters including whole blood viscosity, erythrocyte aggregation and the fibrinogen levels in blood of T3-induce hyperthyroidism rats were higher than those of the group with normal control. Under the observation of the phase-contrsat MRI, it shows that the blood flow of carotid arteries of hyperthyroidism rats were slowly than the normal control group. In addition, our experimental result finds that the brain tissue, hippocampus of hyperthyroidism rats arise a great quantity of malondial dehyde production, at the same time to the normal control group, the antioxidant molecule, glutathione knows a large amount of reduction. Finally, in animal behavioral test also to know: A rat with hyperthyroidism causes anomaly in hemorheological and its learning ability is worse than the normal control group.
From all results above, the T3-induced rats come about anomalies in hemorheological. The anomalies in hemorheological would cause not only the oxidative damage of brain but also the production of malondial dehyde and the glutathione depletion in hippocampus. In addition, it would cause the impaired spatial performance and hinder the memory study processes in Morris water maze and Eight-arm radial maze of rats.
中文摘要 i
英文摘要 iii
誌謝 v
目錄 vi
表目錄 viii
圖目錄 ix
第一章 緒論 1
1.1 前言 1
1.1.1甲狀腺素在人體的生理意義 1
1.1.2甲狀腺素受體(Thyroid Hormone Receptors) 3
1.1.3甲狀腺荷爾蒙反應位元(Thyroid Hormone Response Element) 5
1.1.4 纖維蛋白原 (Fibrinogen) 5
1.1.5 纖維蛋白原基因之調控 6
1.1.6 T3與Fibrinogen的相關係 7
1.1.7 T3調控血液凝集相關因子 8
1.1.8 T3調控纖維蛋白原之分子機制 9
1.2血液流變之異常現象 10
1.2.1血液的組成 10
1.2.2 血液流變 10
1.2.3 血液流變學參數的檢測原理 11
1.2.4 影響血漿黏度之因素 13
1.2.5 影響血液黏度之因素 14
1.2.6血液中氧氣的運輸 15
1.3 血液流變異常與常見臨床腦血管疾病之相關係 16
1.3.1 腦血管疾病概論 16
1.3.2 血液流變異常造成腦血管循環之病理 17
1.3.3 腦缺血對神經傳導造成退化的影響 17
1.3.4 腦缺血造成氧化損傷之機制 19
1.4腦部的記憶與學習 22
1.4.1海馬迴 22
1.4.2腦缺血與學習記憶之關係 23
1.4.3大鼠學習記憶之行為測試 24
1.5核磁共振造影(MRI) 26
1.5.1相位對比成像(Phase- contrast imaging)之原理 26
第二章 研究動機 28
第三章 材料與方法 29
3.1 實驗動物 29
3.2 實驗試藥 29
3.3 實驗儀器 30
3.4 實驗流程圖 35
3.5 實驗流程 36
第四章 結果 42
4.1血液生化值之檢測 43
4.1.1 血液中之Triiodothyronine(T3)與纖維蛋白原(Fibrinogen)之含量 43
4.1.2 全血球計數(Complete blood count,CBC) 44
4.1.3紅血球聚集度 45
4.1.4全血黏度 46
4.1.5氧氣運輸效率(Oxygen transport efficiency,TE) 47
4.1.6 MRI相位對比測量大鼠頸動脈之血流 48
4.2動物行為測試 49
4.2.1水迷宮之比較 49
4.2.2 放射狀八爪迷宮之比較 50
4.3腦組織氧化標的物MDA及GSH濃度之測定 51
第五章 討論 52
5.1三碘甲狀腺素對血液中生化參數值之影響 52
5.2利用三碘甲狀腺素誘發大鼠產生血液流變異常之現象 53
5.3血液流變異常對腦血管造成之影響 55
5.4血液流變異常造成腦組織之氧化損傷 57
5.5血液流變異常對腦部記憶所造成之影響 58
第六章 結論與未來展望 60
參考文獻 62






表目錄

表 4.1 控制組(Control)以及實驗組( T3 ) 全血球計數的值..............................44
表 4.2 控制組(Control)以及實驗組( T3 ) 全血黏度之比較...............................46
表4.3 控制組(Control)以及實驗組( T3 )水迷宮行為測試之之比較..................49
表4.4 控制組(Control)以及實驗組( T3 )放射狀八爪迷宮行為測試之之比較...50

















圖目錄

圖1.1 甲狀腺荷爾蒙合成示意......................................................................... .2
圖 1.2 Deiodination of T4 to T3 and reverse T3............................................ .2
圖1.3 Steroid/thyroid hormone receptor superfamily...........................................4
圖1.4 TR 之structure 與 function domain........................................................4
圖1.5 Fibrinogen 之分子結構............................................................................6
圖1.6 全血黏度與剪切率之函數關係圖.............................................................11
圖 1.7 全血雷射反向散射強度和時間關係圖.....................................................13
圖1.8 全血黏度與血比容..................................................................................14
圖 1.9 ischemic cascade......................................................................................18
圖1.10 海馬迴的構造.......................................................................................23
圖3.1 黏度儀....................................................................................................30
圖 3.2 Laser-assisted optical rotational cell analyser..........................................31
圖3.3 水迷宮....................................................................................................32
圖3.4 放射狀八爪迷宮....................................................................................33
圖3.5 斷頭檯...................................................................................................33
圖3.6 手持式超聲波處理器............................................................................34
圖3.7 核磁共振造影.......................................................................................34
圖3.8 放射狀八爪迷宮....................................................................................37
圖 4.1 控制組(Control)以及實驗組(T3)血液中T3以及Fibrinogen之總含量…43
圖 4.2 控制組(Control)以及實驗組(T3)血液中紅血球聚集度之比較.................45
圖 4.3控制組(Control)以及實驗組( T3 )氧氣運輸效率之比較(Oxygen transport efficiency) ................................................................................................47
圖 4.4控制組(Control)以及實驗組(T3)MRI相位對比測量頸動脈血流速之比較....……………………………………………………….................................................48
圖 4.5 控制組(Control)以及實驗組( T3 ) 腦組織氧化標的物Glutathione(GSH)及
MDA 濃度之比較..................................................................................51
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