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研究生: 謝凱峰
Hsieh Kai-Feng
論文名稱: 比較不同器官及品系的老鼠在全身放射線照射後其發炎反應相關細胞激素的表現
Organ and species in radiation-induced pro-inflammatory cytokines expression following whole body irradiation
指導教授: 江啟勳
Chiang Chi-Shiun
洪志宏
Hong Ji-Hong
口試委員:
學位類別: 碩士
Master
系所名稱: 原子科學院 - 生醫工程與環境科學系
Department of Biomedical Engineering and Environmental Sciences
論文出版年: 2005
畢業學年度: 93
語文別: 中文
論文頁數: 49
中文關鍵詞: 放射線品系器官發炎反應
外文關鍵詞: radiation, specie, organ, inflammatory, cytokine
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  • 在目前癌症治療上,對於某些特定的腫瘤,放射線是常見的治療方式之一。放射線的優點在於可以針對一限制區域的腫瘤進行治療,但治療的過程中還是無法避免照射到正常的組織細胞。當細胞受到放射線的照射後,可能會表現出不同程度和型態的反應,如發炎及免疫反應。目前文獻資料中還沒有放射線與正常細胞的基因表現相關的研究,因此我們首先想了解正常細胞在受到放射線照射後,其免疫相關基因在短時間內的改變。另外我們同時也可以觀察不同型態功能的器官,受到放射線照射後其免疫反應的不同。實驗中我們以C57BL/6J老鼠為實驗對象,分別觀察在放射線的照射後,其八種器官(包括:腦、肺臟、肝臟、腎臟、胰臟、小腸、膀胱和前列腺)在不同時間點上免疫相關基因表現上的改變。另外,我們以注射LPS引發免疫系統反應的C57BL/6J老鼠作為實驗的對照組。從實驗中我們發現,C57BL/6J老鼠在放射線照射後,其腎臟、膀胱和前列腺這三個器官在我們欲觀察的免疫相關基因表現上,和控制組比較起來沒有明顯差異。在腦、肺臟、肝臟、胰臟和小腸等五個器官,分別在TNF-alpha、IL-5、IL-1alpha、INF-gamma、IL-1beta和IL-6的基因表現上都有不同程度改變;其中IL-1beta則是唯一在五種器官均有改變的。根據這樣的結果,我們可以進一步改善在照射治療後,降低老鼠體內引發過度的免疫反應,使細胞可以維持正常的生理功能。


    Radiotherapy is a front treatment for many types of cancer. One of its advantages is to target specific tumor site, however under some condition, there are still risks to induce complications in the surrounding normal tissues. The mechanisms of radiation-induced normal tissue damage are complicated and involve different tissue components such as epithelial cell, stromal cells, inflammatory and immune responses. Our previous studies have found induction of pro-inflammatory are involved in early phases of normal tissue responses to radiation. The purpose of this study is to extend our previous observation and compare the short-term induction of pro-inflammatory cytokines in different organs following whole body irradiation.
    We used C57BL/6J mice as an animal model and analyzed gene expression of pro-inflammatory cytokine in eight organs (brain, lung, liver, kidney, spleen, intestine, bladder and prostate) at different time following whole body irradiation. LPS was used as a positive control for the expression pattern of cytokine genes in a variety of organs following inflammatory stimulation. Among these organs examined, kidney, bladder and prostate did not show induction of pro-inflammatory cytokine genes following irradiation. The other organs including brain, lung, liver, spleen and intestine showed different pattern of TNF-alpha, IL-1alpha, INF-gamma, IL-1beta and IL-6 gene induction, and increase of IL-1beta expression was found in all of these five organs.
    Our studies clearly showed that, in terms of early pro-inflammatory response, different organs respond to radiation damage in a different pattern in their type of cytokine genes, time of expression and intensity of expression. These results provide important information in our understanding radiation-induced early pro-inflammatory responses in different normal tissues.

    英文摘要 ••• I 中文摘要 ••• II 誌謝 ••• III 目錄 ••• IV 第一章 序論 ••• 1 第二章 實驗分組與材料方法 ••• 8 2.1 觀察以TBI處理的C57BL/6J and C3H老鼠之免疫相關基因表現 ••• 8 2.2 觀察以LPS注射處理的C57BL/6J老鼠之免疫相關基表現 ••• 8 2.3 實驗動物來源與飼養 ••• 8 2.4 全身放射線照射 ••• 9 2.5 核甘酸萃取 ••• 9 2.6 RNA Protection Assay ••• 11 2.7 LPS Source and Function ••• 15 第三章 實驗結果 ••• 16 3.1 C57BL/6J老鼠在注射LPS後,八種器官中細胞的發炎相關基因表現 ••• 16 3.2 比較TBI和LPS處理後,在C57BL/6J老鼠中,八種器官的發炎相關基因表現 ••• 17 3.3 比較TBI和LPS處理後,在C3H/HeN老鼠中,八種器官的發炎相關基因表現 ••• 17 3.4 C57BL/6J老鼠在接受全身照射8Gy後,八種器官中細胞的發炎相關基因表現 ••• 17 3.5 C3H/HeN老鼠在接受全身照射8Gy後,八種器官中細胞的發炎相關基因表現 ••• 19 3.6 在TBI處理之後,比較C57BL/6J和C3H/HeN兩種不同品系老鼠中,八種器官的發炎相關基因表現 ••• 20 第四章 討論 ••• 21 第五章 實驗結果圖表 ••• 26 圖一 RPA of Brain, Lung, Liver and Kidney of LPS-injected C56BL/6J Mice ••• 26 圖二 RPA of Spleen, Intestine, Bladder and Prostate of LPS-injected C56BL/6J Mice ••• 27 圖三 RPA of Brain of TBI C57BL/6J Mice ••• 28 圖四 RPA of Lung of TBI C57BL/6J Mice ••• 29 圖五 RPA of Liver of TBI C57BL/6J Mice ••• 30 圖六 RPA of Spleen of TBI C57BL/6J Mice ••• 31 圖七 RPA of Intestine of TBI C57BL/6J Mice ••• 32 圖八 RPA of Kidney of TBI C57BL/6J Mice ••• 33 圖九 RPA of Bladder of TBI C57BL/6J Mice ••• 34 圖十 RPA of Prostate of TBI C57BL/6J Mice ••• 35 圖十一 RPA of Prostate of TBI C57BL/6J Mice ••• 36 圖十二 RPA of Prostate of TBI C57BL/6J Mice ••• 37 圖十三 RPA of Prostate of TBI C57BL/6J Mice ••• 38 圖十四 RPA of Prostate of TBI C57BL/6J Mice ••• 39 圖十五 RPA of Prostate of TBI C57BL/6J Mice ••• 40 表一 比較LPS注射C57BL/6J老鼠4小時後的免疫相關基因表現••• 41 表二 比較C57BL/6J老鼠在全身照射後,不同時間點上免疫相關 基因的表現 ••• 42 表三 比較C3H/HeN老鼠在全身照射後,不同時間點上免疫相關基 因的表現 ••• 44 表四 比較C57BL/6J和C3H/HeN兩種品系的老鼠,在放射線照射 後,不同時間點及器官的發炎反應相關基因表現 ••• 45 第六章 參考文獻 ••• 46

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