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研究生:謝昇宏
研究生(外文):Sheng-Hung Hsieh
論文名稱:以超順磁性氧化鐵奈米粒子增強功能性磁共振造影的影像用於潛伏性結核病的早期偵測
論文名稱(外文):Early detection of latent tuberculosis using super-paramagnetic iron oxide nanoparticle enhanced functional magnetic resonance imaging
指導教授:賴文福賴文福引用關係
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:醫學科學研究所
學門:醫藥衛生學門
學類:醫學學類
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:55
中文關鍵詞:結核病分子影像SPIO-Tb-Ab磁振造影肺外結核BCG
外文關鍵詞:tuberculosismolecular imagingSPIO-Tb-AbMRIextra-pulmonary tuberculosisBCG
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結核病從古自今一直是威脅人類健康的疾病之一,也是現今全球死亡率最高的三種傳染性疾病之一。自從1990年中期以後,原本被認為會漸漸走入歷史的結核病又有死灰復燃的跡象,而且不論是發生率或死亡率都有逐年增加的趨勢。現今全球大約有3分之1的人口感染結核病,而且每年平均約有2-3百萬人死於此疾病。為了要有效的除去此威脅,除了平時常保健康的身體和營養充足外,對於準確的診斷和有效的治療也是消滅結核病的重要方法之一。
本研究主要的目的在於嘗試提供一種新的結核病的診斷方式,藉由分子影像可以表現出細胞/分子這層次細微變化的特性,結合本實驗室所設計的結核桿菌專一性探針-SPIO-Tb-Ab,以磁振造影(MRI-magnetic resonance imaging)非侵入性的影像呈現方式做為診斷的儀器,利用此專一性探針來捕捉並同時增強影像的效果,希望可以用來達到早期診斷潛伏期的結核病和肺外結核的部分。
我們將傳染性較弱的減毒疫苗BCG(Bacille Calmette-Guérin)種在老鼠背部皮下,並將SPIO-Tb-Ab從尾靜脈打入老鼠體內,利用3.0T MRI進行觀察。我們在注射BCG的部位可以發現到有MRI訊號的產生,利用組織染色的方法在相同部位可以發現到SPIO-Tb-Ab染色的結果,證明MRI訊號的產生確實是由SPIO-Tb-Ab所引起的,而在其他部位則看不到MRI訊號產生。因此我們認為利用SPIO-Tb-Ab結合MRI的方法也許可以提供一種診斷結核病的方法。
Tuberculosis is one of the threatening human diseases anciently from today, and also the one of the top three global infective disease killers. Since mid 1990, originally thought the TB would soon be consigned to the pages of history gradually has sign reviving, and no matter the incidence or mortality all have the tendency to increase year by year. One-third of the population is infected with the tuberculosis in the world now, and there are 2-3 million people die of this disease every year. In order to effective removing this threat, except the often protect the health and sufficient nutrition all the times, to accurate diagnosis and effective treatment is one of the important methods to eliminate the tuberculosis.
The main purpose of this research is trying to provide a kind of new tuberculosis diagnosis method. According to the molecular imaging character, it can in vivo characterization and measurement of biologic processes at the cellular and molecular level. We use the noninvasive in vivo magnetic resonance imaging 2 as a detection instrument combine with Mycobacterium tuberculosis specific probe SPIO-Tb-Ab (super-paramagnetic iron oxide-tuberculosis-antibody), catching and strengthening the image at the same time. We hope this diagnosis method cans being used for detection latent tuberculosis and extra-pulmonary tuberculosis in early days.
We planted the attenuated vaccine BCG (Bacille Calmette-Guerin) on mouse back by subcutaneous injection and then intravenous injection with SPIO-TB-Ab for 3.0T MR imaging. We found there is a MRI signal in the injection site and the results is coincident with the tissue section stain. According to the results, we think this method of utilizing the idea of the molecule image to combine MRI instrument perhaps can offer a kind of new diagnosis method to tuberculosis.
中文摘要
英文摘要
第壹章 緒論
一、 結核病的概論.....................1
(1)結核病的歷史........................1
(2)結核病的流行病學....................3
(3)結核桿菌的形態與特性................3
(4)結核病的病理學和致病機制............4
二、 結核病的診斷方法.................7
(1)傳統的診斷方法......................7
(2)非傳統的診斷方法....................9
三、 分子影像.........................13
(1)核子造影............................14
(2)光學造影............................15
(3)磁共振造影..........................16
(4)電腦斷層掃描........................18
第貳章 實驗目的...........................20
第参章 材料與方法
一、細胞株與動物..........................21
二、結核桿菌抗原、抗體和牛分枝桿菌的選用..21
三、細胞培養..............................21
四、SPIO-Tb-Ab合成........................22
五、柏林藍染色法..........................23
六、抗酸菌染色法..........................23
七、動物實驗..............................23
八、組織切片及染色........................25
九、免疫組織染色..........................26
第肆章 實驗結果
一、利用染色來証實SPIO-Tb-Ab和結核桿菌間的專一性................................28
二、以磁振造影觀察BCG和SPIO-Tb-Ab作用後的變化..................................28
三、以THP-1當作細胞模型來模擬體內巨噬細胞吞噬結核桿菌的生理情形,並
觀察細胞內的SPIO-Tb-Ab對於磁振造影之影像的變化............................29
四、結核桿菌動物模型...........................................................................................29
五、觀察SPIO-Tb-Ab在老鼠體內分佈情形和對磁振造影的影響.....................30
六、各種不同時間點上對於磁振造影的觀察.......................................................30
七、利用組織染色來証實磁振造影的結果...........................................................31
第伍章 討論.............................32
第陸章 參考文獻.........................37

圖一、結核桿菌與鐵離子的染色.....................43
圖二、利用磁振造影觀察BCG和SPIO-Tb-Ab間的作用....44
圖三、利用THP-1當作細胞模型,觀察細胞內的SPIO-Tb-Ab對於磁振造影之影像的變化.................................45
圖四、觀察BCG種在老鼠皮下的組織形態和免疫染色....46
圖五、活體內磁振造影的觀察.......................49
圖六、不同時間點上對於磁振造影訊號改變的觀察.....50
圖七、免疫組織染色的觀察.........................52

附錄
附錄一、結核桿菌的形態和痰抹片染色...............55
附錄二、發展活體分子生物影像的關鍵...............55
附錄三、結核桿菌細胞壁的成分.....................55
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